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Wong, Wan Yee. "Solvothermal crystallization of organic compounds and natural products /." View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202006%20WONG.
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Cowe, H. J. de L. "Molecular studies of natural products and related compounds." Thesis, Robert Gordon University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370758.
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Atkinson, A. M. "Structures of some natural products and metallo-organic compounds." Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/46946.
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Hussain, Amjad. "The synthesis of heterocyclic compounds related to natural products." Thesis, Swansea University, 2001. https://cronfa.swan.ac.uk/Record/cronfa43039.
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The thesis relates to the synthesis of heterocyclic compounds related to Natural Products. Chapter 1 deals with an introduction to hypervalent iodine reagents and their uses as phenolic oxidation reagents. The mechanism is also discussed. Chapter 2 concentrates on the production of 3-substituted phenols and the subsequent hypervalent iodine oxidation to see if a variety of chromenone compounds can be formed via intramolecular attack. Whilst not successful in generating the desired compounds, a number of oxidised products were isolated. Chapter 3 deals with making the 3-nucleophilic side chain on various phenols more rigid in the hope of aiding cyclisation. One reaction of note from this chapter was that an epoxide ring utilised, to give rigidity in the side chain, withstood the hypervalent iodine oxidation. Chapter 4 utilises the epoxide to bring rigidity to the 3-substituted side chain. All products bar one proved successful in generating their appropriate epoxychromenes, and that which didn't provided an alternative cyclised product. The final chapter deals with possible future work now that some success has been achieved.
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Dengada, Amrapali Harishkumar. "Isolation and Structural Elucidation of Compounds from Natural Products." Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/64303.
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Isolation and Structural Elucidation of Compounds from Natural Products
Amrapali H. Dengada
In continuation of the Kingston group's work to identify new compounds from natural products as a part of the International Cooperative Biodiversity Group (ICBG) program and in collaboration with the Institute for Hepatitis and Virus Research (IHVR), the two plants Neoharmsia baronii and Lopholaena cneorifolia were studied to identify their chemical components. Structural elucidation and characterization of the compounds were done using mass spectrometry, 1D and 2D NMR spectroscopy techniques.
A systematic study of the ethanol extract of the plant Neoharmsia baronii Drake from the Madagascar forest led to the isolation of seven compounds, characterized as isoflavones and pterocarpans. The structures of the compounds were characterized by using 1D NMR and 2D NMR spectra, mass spectroscopy and in one case, x-ray crystallography. The HSQC and HMBC data along with comparison of these data with reported literature values confirmed the structures. The aforementioned isoflavones and pterocarpans showed varying cytotoxicity to ovarian cancer cell lines, with the isoflavone vogelin E being the most active compound.
The extract of Lopholaena cneorifolia was studied as a part of a cooperative project with the IHVR to identify its chemical composition. Fractionation of this extract led to the isolation of three compounds which were characterized as stilbenes. Their structures were elucidated by using 1D NMR and 2D NMR spectra and mass spectroscopic data.Master of Science
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Fabiano, E. "Synthesis and reactions of amino compounds relating to natural products." Thesis, University of Newcastle Upon Tyne, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373890.
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Reddy, P. S. "Synthesis of some biologically active compounds and some natural products." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 1986. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/3261.
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Heltzel, Carl E. "Structural and synthetic studies of bioactive natural products." Diss., Virginia Tech, 1993. http://hdl.handle.net/10919/40067.
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Bioassay directed fractionation of the methyl ethyl ketone extract of Crescentia cujete resulted in the isolation of nine bioactive compounds, and detailed spectroscopic interpretation led to the assignment of their structures as (2S,3S)-3-hydroxy-5,6-dimethoxy dehydroiso-α-Iapachone [2.10], (2R)-5,6- dimethoxydehydroiso-α-Iapachone [2.11], (2R)-5-methoxy dehydroiso-alapachone [2.12], 5-hydroxy-2-(1'-hydroxyethyl)naphtho[2,3-b ]furan-4,9-dione [2.13], 2-(1 '-hydroxyethyl)naphtho[2,3-b ]furan-4,9-dione [2.14]' 2-isopropenylnaphtho[ 2,3-b ]furan-4,9-dione [2.15], 5-hydroxydehydro-iso-a-Iapachone [2.16], 3-hydroxymethylfuro[3,2-b ]naphtho[2,3-d]furan-5,10-dione [2.17], and 9- hydroxy-3-hydroxymethylfuro[3,2-b ]naphtho[2,3-d]furan-5,10-dione [2.18]. Compounds 2.10-2.12 are new, showing selective activity towards DNA repair-deficient yeast mutants. The selective DNA damaging activity of known compounds 2.13-2.16 is reported herein for the first time. Compounds 2.17 and 2.18 also show DNA damaging activity, and possess a novel fused ring system.
The bioactive sterols ergosta-5-24(28)-diene-3β,7α-diol [3.1] and 24,28- epoxyergost-5-ene-3β,7α-diol [3.2], originally isolated from Pseudobersama mossambicensis, have been synthesized from stigmasterol. In addition to these sterols, some of their analogs were prepared, and the bioactivity of all compounds were assessed.Ph. D.
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Marucci, C. "NATURAL PRODUCTS AS BUILDING BLOCKS AND LEAD COMPOUNDS FOR API PRODUCTION." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/480029.
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This dissertetion describes the relevance of natural products as building blocks for production of active pharmaceutical ingredients (API) and as lead compounds.
Chapter 1 offers an introduction on the use of natural products as an effective therapeutic and its role on inspiring the discovery of new drugs.
Chapter 2 focuses on the importance of natural products as lead compounds for active pharmaceutical ingredients (API) production. In the first part of this chapter the synthesis of vincamine, the major indole alkaloid presents in Vinca minor L., will be discussed. In particular the design of experiment (DOE) applied to the synthesis of vincamine starting from vincadifformine will be described. In the second part of this chapter the semi-synthesis of two lignan derivatives, oxomatairesinol and (-)-7-(R)-hydroxymatairesinol, will be reported.
Chapter 3 will focus on the isolation and structural characterization of natural products. The first part describes the isolation and structural characterization of ten indole alkaloids from Voacanga africana (Apocynaceae) seeds. Then the semisynthesis of two cytisine derivatives, N-formyl and N-methyl cytisine, will be described.
Chapter 4 describes the role of natural products as lead compounds. The first section illustrate a project that was performed in the laboratory of Prof. Karl-Heinz Altmann (ETH-Zurich, Switzerland) in the frame of COST Action CM1407 (Challenging Organic Synthesis Inspired By Nature: From Natural Product Chemistry To Drug Discovery). It is related to the synthesis of an analogue of the natural product doliculide, a 16-membered depsipeptide, that has been isolated in 1994 from the Japanese sea hare Dolabella auricularia. The second section will focus on the design and synthesis of hybrid compounds. Particularly it will describe the synthesis of pironetin-dumetorine hybrid compounds whose structures are representative of an optimizable lead scaffold for the discovery of new tubulin binders. Another topic here discussed will be the production of bivalent compounds linking two different units, a pironetin-dumetorine hybrid compound and a drug able to bind beta-tubulin, in order to have a duble action with the aim to limit the the protein-protein interaction between alfa and beta tubulin.
Chapter 5 offers an overview on the role of natural products in drug discovery, in particular related to cancer stem cells (CSCs). In a recent review we summarized the natural products that demonstrate activity against CSCs. Forty-nine different natural products grouped into several structural classes (such as flavonoids, polyketides, terpenes, alkaloids and many others) will be described. Their structure diversity could suggest the synthesis of libraries of new compounds for a huge exploration of the chemical space of CSCs inhibitors.
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Sun, Lin. "Application of New Technologies for the Rapid Identification of Compounds from Natural Sources." Thesis, University of Canterbury. Chemistry, 2009. http://hdl.handle.net/10092/4188.
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This thesis represents a continuation of the work on the isolation and
structure elucidation of potential drug leads from terrestrial fungal sources
that the natural products group at the University of Canterbury has been
engaged in.
Capillary NMR spectroscopy was involved in the research as the main tool
for dereplication and elucidating the structures of novel bioactive
compounds as well as for biosynthetic studies.
Eleven new compounds including five cyclic peptides, four related pyrones
and two diketopiperazines were isolated from the extract of Aspergillus sp.
of endophyte collected from Malaysia. The five peptides F8268-A-1 to
F8268-A-5 showed excellent P388 (HCT116 (ATCC CCL-247) and human
breast cancer, MCF7 (ATCC HTB-22)) activities. Two of the peptides
F8268-A-3 and F8268-A-5 were 4,000 times more active when compared
with commercial drugs (fluorouracil, cisplatin and tamoxifen). The partial
stereochemistries of F8268-A-2 and F8268-A-3 were established by
Marfey’s method.
Four related pyrones isolated from the same extract were also shown to have
good P388 activities. They are related to the known compound NF00659A3.
The relative stereochemistries were established from NOSEY experiments
and the energy-minimised (MM2) model created using CHEM 3D software.
Two new diketopiperazines, F7474-D3 and F7474-D11, also isolated from
the Aspergillus extract did not show activity in the P388 assay. F7474-D11
contained the amino acid Me-kynurenine which is the first report of this
from a natural source. The absolute stereochemistry of F7474-D11 was
elucidated by Marfey’s method. The other diketopiperazine F7474-D3 was similar to the known compound lumpidin, and combined use of ROESY
NMR and Marfey’s method established that the constituent amino acids had
the unusual R configuration.
Dereplication has been greatly improved by the application of capillary
NMR. For example, the HPLC analysis and UV library searching of
compounds from extracts F8095 and F7855 suggested they contained related
compounds belonging to the lasiodiplodin family. However, CapNMR
spectroscopic analysis and AntiMarin database searching revealed that the
compounds from F8095 were all known polyesters while the compounds
from F7855 did belong to the lasiodiplodin family. Two new lasiodiplodins
were found in the F7855 extract,
(3R,4R)-4-hydroxy-de-O-methyl-lasiodiplodin (F7855-4) and
(E)-9-etheno-de-O-methyl-lasiodiplodin (F7855-6). The relative
stereochemistries were elucidated from NMR coupling constant analyses.
Two new dimers (F7090-A and F7090-B) were elucidated from a New
Zealand fungal endophyte. The differences between these two dimers was
their stereochemistries. F7090-A had the same stereochemistries for the
three stereocentres in both parts, while the stereochemistry of F7090-B was
different in the two parts of the dimer.
Biosynthetic studies were also carried out using CapNMR methodology. A
known compound tetrahydrofuran A and a new compound tetrahydrofuran B
from an unidentified New Zealand fungus were used for this study. For the
first time an INADEQUATE NMR experiment was successfully carried out
using CapNMR spectroscopy, thus demonstrating the capability for carrying
out biosynthetic studies on a very small scale (<200 μg of ¹³C-labelled
compound). The implementation of efficient dereplication procedures with CapNMR
methodology is paramount for those working in the field of natural products.
The recent advances that have been made in the dereplication process in the
natural products group at the University of Canterbury are given using
examples from this research and where necessary from other group
members.
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Arnold, Megan. "Investigating natural products as new drug leads for malaria." Thesis, Griffith University, 2018. http://hdl.handle.net/10072/381398.
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Despite being preventable and treatable, malaria continues to be a significant threat to global health, particularly in the developing world. It is estimated that 90% of all malaria deaths occur in Africa and that 78% of these deaths occur in children under five years of age due to infection with Plasmodium falciparum malaria parasites. While malaria control strategies, together with the global malaria eradication agenda, has resulted in a 48% decline in global malaria mortality rates over the past decade, progress has stalled. A recent rise in malaria cases is particularly concerning given the development of parasite resistance to currently used antimalarial drugs, including the gold standard artemisinin combination therapies (ACTs). Until recently, anti-malarial drug discovery efforts have focused on fast-acting compounds that kill parasites quickly to relieve symptoms. However, the goal to eradicate malaria, has meant that in addition to treatment drugs, preventative measures, including a broadly effective vaccine, vector control strategies and chemoprophylactic drugs are needed. Currently, all drugs that are prescribed for chemoprophylaxis are also used for treatment, a situation which can impact drug resistance selection particularly given prophylactic drugs are often prescribed for weeks to months at a time, increasing the potential for drug resistant parasites to develop.
The focus of this project was to identify compounds with chemoprophylactic potential that have a different mode of action to currently used treatment drugs. As chemoprophylactic drugs do not necessarily need to kill parasites quickly, compounds with a slow-action phenotype were investigated as they are likely to have mechanisms of action distinct from fast-acting treatment drugs. In this project a subset of compounds from Griffith University’s Nature Bank were tested for slow-action antimalarial potential using P. falciparum [3H]-hypoxanthine incorporation in vitro growth inhibition assays.
From a primary screen of 524 pure compounds and 424 fractions, 36 pure compounds and 1 fraction were identified as slow-action hit compounds. Two compounds (alstonine and himbeline) were identified that met pre-defined criteria of potency (50% inhibitory concentration (IC50) <1 μM) against P. falciparum 3D7 parasites and selectivity for parasites over two mammalian cell lines (NFF and HEK 293; Selectivity Index (SI) >100 μM).
Additional studies using phenotypic approaches were carried out to investigate the activity of alstonine and himbeline against P. falciparum parasites. Known slow-action/ “delayed death” mechanisms of action were first investigated to determine if alstonine and himbeline had novel mechanisms of action. Neither alstonine or himbeline treated parasites were rescued by the supplementation of isopentyl pyrophosphate (IPP) indicating that they have a mode of action independent of the P. falciparum apicoplast and therefore have different targets to compounds which are known to inhibit this pathway such as clindamycin and fosmidomycin. Alstonine and himbeline were also found to have no-cross resistance with several P. falciparum lines with resistance to clinical drugs including chloroquine (Dd2; FCR3), atovaquone (C2B) and cycloguanil (FCR3). Interestingly, C2B parasites which are resistant to atovaquone via a mutation in cytochrome bc1 were hypersensitive to alstonine. P. falciparum parasites expressing yeast dihydroorotate dehydrogenase (3D7-yDHODH) that are resistant to PfDHODH inhibitors and have reduced susceptibility to compounds that target the mitochondrial electron transport chain (mtETC) were used to investigate the involvement of alstonine with these pathways. 3D7-yDHODH parasites were shown to be 15-fold less sensitive to alstonine indicating that the activity of this compound may be associated with mitochondrial function or the pyrimidine biosynthetic pathway.
Stage specific wash off experiments were carried out to better understand whether ring versus trophozoite stages might be more susceptible to alstonine or himbeline. Alstonine and himbeline both inhibited trophozoite stage parasites faster than ring stages, indicating that while the compound’s action against parasites occurs within the first asexual intraerythrocytic developmental cycle, the inhibitory effect is only observed in the second cycle. Previous studies have identified compounds with similar slow action phenotypes that also show similar stage specific phenotypes. For example, antifolate compounds such as pyrimethamine and sulfadoxine which are less effective when treating ring stage than trophozoites. In other studies, cytochrome bc1 inhibitors such as atovaquone display slow action activity and trophozoites are also most susceptible to treatment. Although nondefinitive, these data indicate that folate biosynthesis or the mtETC could be potential targets for alstonine or himbeline.
To further investigate the action of alstonine and himbeline, P. falciparum 3D7 parasites were selected for resistance to each compound for ~200 days. While a himbeline resistant line was not able to be obtained, an alstonine resistant line was generated (3D7-C3ALST) which had a 14-fold lower IC50 than the parental line 3D7-C3. A panel of antimalarial control compounds including chloroquine, atovaquone, proguanil, cycloguanil, clindamycin and himbeline was then tested against 3D7-C3ALST and no cross-resistance was observed. Interestingly, 3D7-C3ALST was found to be hypersensitive to atovaquone and proguanil, two compounds which evidence suggests inhibit Plasmodium parasites via the mtETC. These data provided further evidence of alstonine’s association with the mtETC.
In conclusion, information presented in this thesis has shown that slow-action antiplasmodial compounds could be identified from Nature. Alstonine and himbeline each satisfied the hit-like potency and lead like-selectivity criteria outlined by the Medicines for Malaria Venture, the global authority on target candidate profiles for malaria drug candidates. No apparent cross-resistance with drug resistant lines was observed. In addition, data indicate that alstonine likely has a mechanism of action against P. falciparum parasites via the mtETC or pyrimidine biosynthesis, priming further studies to define the mechanisms of action of this compound. This work paves the way for additional studies on these early phase drug leads, including synthesis and testing of more potent and selective analogues, further mode of action studies and, if warranted in vivo studies to ascertain in vivo efficacy in mouse malaria models.Thesis (Masters)
Master of Philosophy (MPhil)
School of Environment and Sc
Science, Environment, Engineering and Technology
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Zhang, Yanan. "Approaches to the total synthesis of the lamellarins and related natural products." Diss., Online access via UMI:, 2005.
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Sutivisedsak, Nongnuch. "Synthesis of [alpha]-hydroxy and fluoro phosphonates and cyclic ether-containing natural products." Diss., St. Louis, Mo. : University of Missouri--St. Louis, 2008. http://etd.umsl.edu/r3246.
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Sheth, Ritesh B. "Development of new synthetic methodologies and the synthesis of natural products." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 101 p, 2010. http://proquest.umi.com/pqdweb?did=1993336351&sid=2&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Dowle, Katie Orlagh. "New nitrogenous spongian diterpenes from the New Zealand marine sponge Darwinella oxeata : a thesis submitted to the Victoria University of Wellington in fulfilment of the requirements for the degree of Master of [Science] in Chemistry /." ResearchArchive@Victoria e-Thesis, 2008. http://hdl.handle.net/10063/626.
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Han, Jianying. "Exploring the Potential of Endophytes and Fungi as Sources of Antimicrobial Compounds." Thesis, Griffith University, 2021. http://hdl.handle.net/10072/404851.
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Microbes are leading producers of numerous active natural products, many of which have been developed as antibiotics, anticancer agents, and immunosuppressants. The importance and significance of microbial natural products was recognized by the Nobel Prizes in Physiology or Medicine awarded for discovery of penicillin, streptomycin, and avermectin in 1945, 1952 and 2015, respectively. The high occurrence of drug resistance and the high rate of re-isolation represent new challenges. In order to respond to the current challenges and meet the urgently clinical need, new approaches are required to exploit new sources from under-explored habitats and their biosynthetic potentials. This thesis presents efforts to investigate antimicrobial natural products from fungi and endophytes with the combination of genome mining, NMR fingerprint HRMS, and HRMS/MS.
The thesis begins with a review on recent advances on anti-TB natural products (NPs) and their potential molecular targets (Chapter 1). 53 natural products showing antimycobacterial activity with defined molecular targets were summarized. Compounds with activity against drug-resistant TB (thiolactomycin, pyridomycin, novobiocin, lipiarmycin A3, gladiolin, kanglemycin A, (S)-(−)-acidomycin, ecumicin, lassomycin, and cyclomarin A) and novel targets (Mtb biotin synthase, ATP synthase, 1,4-dihydroxy-2-naphthoate prenyltransferase, biofilm) were highlighted.
Chapter 2 reports on genome- and MS-based investigation of chlorinated compounds from the phytopathogenic fungus Bipolaris sorokiniana 11134 (BS11134). MS- and UV-guided isolation and purification led to the identification of six new compounds together with seven known xanthones. The biosynthetic gene cluster and putative biosynthetic pathway of isolated compounds were proposed. New chlorinated compound methyl 4-chloro-3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate showed activity against Staphylococcus aureus, methicillin-resistant S. aureus, and three clinical-resistant S. aureus strains with a shared minimum inhibitory concentration (MIC) of 12.5 μg/mL.
In chapter 3, MS- and UV-guided isolations led to the isolation of ten meroterpenoids from BS11134, including two new compounds 19-dehydroxyl-3-epiarthripenoid A and 12-keto-cochlioquinone A. The stereochemistry difference of aliphatic side chain C-1–C-5 in isocochlioquinone F was proposed to result from stereospecificity of enoyl reductase (ER) of highly reducing polyketide synthase CcqF. Four compounds showed activity against S. aureus and methicillin-resistant S. aureus, with MIC values of 12.5–100 μg/mL. Cochlioquinone B exhibited activity against four clinical resistant S. aureus strains and synergistic antifungal activity against Candida albicans with MIC values of 12.5–25 μg/mL.
Chapter 4 describes the genome-inspired chemical exploration of the marinederived fungus Aspergillus fumigatus MF071. Two new compounds 19S,20-epoxy-18-oxotryprostatin A and 20-hydroxy-18-oxotryprostatin A, in addition to 28 known compounds, were isolated from MF071. NMR data of monomethylsulochrin-4-sulphate and pseurotin H as naturally occurring compounds were firstly reported. The antibacterial activities of these compounds were evaluated. Helvolinic acid and helvolic acid exhibited strong activity against S. aureus (MIC: 6.25 and 3.13 μg/mL, respectively) and E. coli (MIC: 6.25 and 3.13 μg/mL, respectively). Genomic data analyses revealed the putative biosynthetic gene clusters ftm for fumitremorgins, pso for pseurotins, fga for fumigaclavines, and hel for helvolinic acid.
Finally, chapter 5 describes the analytical method using 1H NMR and HR-LCMS to investigate the chemical profile of microbial co-cultures. A microbial single culture extract and co-culture extract library was constructed and subjected to antimycobacterial activity screening. The chemical investigation of Talaromyces sp. MF059 and Bacillus sp. LF017 co-culture led to the discovery of bacillibactin, one siderophore with catecholic trilactone structure.
In summary, this thesis reports on the isolation and characterization of 67 secondary metabolites from fungi and endophytes, including 10 new compounds. 20 out of 67 showed antimicrobial activities against different bacteria. The structures of isolated compounds were elucidated based on NMR, HRESIMS, density functional theory (DFT) calculation, and DP4 probability analysis. The results show the great biosynthetic capacity of fungi and endophytes to produce diverse active metabolites. This thesis also demonstrates that the unexplored “biosynthetic dark matter” can be discovered using genome mining, HRMS, NMR, HRMS/MS, and co-culture.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
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Strand, Mårten. "The discovery of antiviral compounds targeting adenovirus and herpes simplex virus : assessment of synthetic compounds and natural products." Doctoral thesis, Umeå universitet, Virologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88186.
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There is a need for new antiviral drugs. Especially for the treatment of adenovirus infections, since no approved anti-adenoviral drugs are available. Adenovirus infections in healthy persons are most often associated with respiratory disease, diarrhea and infections of the eye. These infections can be severe, but are most often self-limiting. However, in immunocompromised patients, adenovirus infections are associated with morbidity and high mortality rates. These patients are mainly stem cell or bone marrow transplantation recipients, however solid organ transplantation recipients or AIDS patients may be at risk as well. In addition, children are at higher risk to develop disseminated disease. Due to the need for effective anti-adenoviral drugs, we have developed a cell based screening assay, using a replication-competent GFP expressing adenovirus vector based on adenovirus type 11 (RCAd11GFP). This assay facilitates the screening of chemical libraries for antiviral activity. Using this assay, we have screened 9800 small molecules for anti-adenoviral activity with low toxicity. One compound, designated Benzavir-1, was identified with activity against representative types of all adenovirus species. In addition, Benzavir-1 was more potent than cidofovir, which is the antiviral drug used for treatment of adenovirus disease. By structure-activity relationships analysis (SAR), the potency of Benzavir-1 was improved. Hence, the improved compound is designated Benzavir-2. To assess the antiviral specificity, the activity of Benzavir-1 and -2 on both types of herpes simplex virus (HSV) was evaluated. Benzavir-2 displayed better efficacy than Benzavir-1 and had an activity comparable to acyclovir, which is the original antiviral drug used for therapy of herpes virus infections. In addition, Benzavir-2 was active against acyclovir-resistant clinical isolates of both HSV types. To expand our search for compounds with antiviral activity, we turned to the natural products. An ethyl acetate extract library was established, with extracts derived from actinobacteria isolated from sediments of the Arctic Sea. Using our screening assay, several extracts with anti-adenoviral activity and low toxicity were identified. By activity-guided fractionation of the extracts, the active compounds could be isolated. However, several compounds had previously been characterized with antiviral activity. Nonetheless, one compound had uncharacterized antiviral activity and this compound was identified as a butenolide. Additional butenolide analogues were found and we proposed a biosynthetic pathway for the production of these compounds. The antiviral activity was characterized and substantial differences in their toxic potential were observed. One of the most potent butenolide analogues had minimal toxicity and is an attractive starting point for further optimization of the anti-adenoviral activity. This thesis describes the discovery of novel antiviral compounds that targets adenovirus and HSV infections, with the emphasis on adenovirus infections. The discoveries in this thesis may lead to the development of new antiviral drugs for clinical use.
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Khan, Ashna Ashneen. "Cascade approaches towards the synthesis of Daphnioldhanin A alkaloid : a thesis submitted to the Victoria University of Wellington in fulfilment of the requirements for the degree of Master of Science in Chemistry /." ResearchArchive@Victoria e-Thesis, 2008. http://hdl.handle.net/10063/818.
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Afolayan, Omolola. "Discovery of antibacterial lead compounds from marine organisms." University of the Western Cape, 2020. http://hdl.handle.net/11394/7914.
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Philosophiae Doctor - PhDMarine organisms including algae and bacteria are known to produce chemically diverse secondary metabolites for survival purposes in the marine environment. Scientists have identified some of these natural products as therapeutic agents including some antibiotics. Given the increase in the resistance of pathogenic microorganisms especially methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis to commonly prescribed antibiotics, researchers have turned towards exploiting marine natural products for new antibacterial compounds. Due to the proven success of finding bioactive compounds in the marine environment this study therefore aims to discover lead compounds against MRSA and Mycobacterium tuberculosis from two marine sources, the marine algae and the bacteria associated with marine invertebrates referred to as bacterial isolates.
2024
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Thwala, Sazi Selby. "Investigation of the natural products composition from the seaweed ulva capensis." University of Western Cape, 2019. http://hdl.handle.net/11394/7888.
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>Magister Scientiae - MScIn modern society, diversity of marine macroalgae has become an inspiration for pharmaceutical companies and researchers because of their numerous health benefits, and a great deal of interest has developed towards the isolation of bioactive compounds to identify novel marine natural products that could eventually be developed into therapeutics or pharmaceutical products. Furthermore, marine macroalgae are valuable source of structurally diverse metabolites with scientifically proven reports. The search continues as there are many natural bioactive compounds that are in the womb of the ocean which are still a mystery. Thus, the present study investigates the natural products from green seaweed Ulva capensis.
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Roberts, Alexandra Anne Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Unnatural production of natural products: Heterologous expression and combinatorial biosynthesis of cyanobacterial-derived compounds." Publisher:University of New South Wales. Biotechnology & Biomolecular Sciences, 2008. http://handle.unsw.edu.au/1959.4/41533.
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Cyanobacteria produce a myriad of structurally unique secondary metabolites with useful bioactive properties. Heterologous expression of a variety of microbial natural compounds has been used to harness their diversity and facilitate their combinatorial biosynthesis. However, these genetic techniques have not been developed for secondary metabolite-producing cyanobacteria. Therefore the genetically manipulable Escherichia coli and Synechocystis sp. PCC6803 were engineered in order to develop effective heterologous hosts and promoters for the expression of cyanobacterial-derived compounds. The phosphopanthetheinyl transferase (PPT), Sppt, from Synechocystis sp. PCC6803 was characterised to determine its ability to activate carrier proteins from secondary metabolite pathways. Despite in silico evidence which suggested Sppt was able to activate a wide range of carrier proteins, biochemical analysis revealed that it is dedicated for fatty acid synthesis. Consequently, E. coli and Synechocystis sp. PCC6803 were engineered to encode a broad-range PPT, from the filamentous cyanobacteria Nodularia spumigena NSOR10, for the activation of carrier proteins from nonribosomal peptide synthesis. Cyanobacterial natural product engineering was also explored with the characterisation of two relaxed specificity adenylation domains (A-domains) from the biosynthetic pathway of the toxin microcystin. The wide variety of microcystin compounds produced by cyanobacterial species suggests that multiple amino acids can be activated by the same A-domain. This was supported by preliminary ATP-[32P]PPi exchange assays and was subsequently harnessed in the production of a variety of dipeptides using two reconstituted modules in vitro. Transposition was investigated as a potential mechanism for the transfer of nonribosomal peptide synthetase gene clusters to heterologous hosts. This was performed via the characterisation of the putative transposase, Mat, physically linked with the microcystin synthetase gene cluster (mcyS). PCR screening, in silico analysis and nitrocellulose filter binding assays indicated that this transposase may have mediated mcyS gene cluster rearrangements but not entire gene cluster mobilisation between species. The potential role of transposases in the natural combinatorial biosynthesis of microcystin has evolutionary implications for the dynamic nature of cyanobacterial genomes and applications for use in the engineering of novel bioactive compounds. Therefore, the results from this study may provide a biotechnological platform for the transfer, expression and combinatorial biosynthesis of novel cyanobacterial-derived natural products.
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Tatton, Matthew R. "New methods for the synthesis of aromatic compounds." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:52a95189-d8ea-432f-aefd-4f9ae7ef996a.
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Introduction The introduction describes the importance of arylamine compounds to society and provides a brief overview of the methods available for their synthesis. The application of metathesis catalysis to the de novo synthesis of heteroaromatic compounds is also described. Results and discussion The first section describes efforts towards the de novo synthesis of arylamines using a cross metathesis/oxidation protocol to form a 1,5-unsaturated dicarbonyl followed by an amine mediated cyclisation. The scope with respect to the 1,5-unsaturated dicarbonyl and amine is covered as well as the utility of some of the products. The section concludes with a modification of the Bohlmann Rahtz pyridine synthesis to furnish arylamines. The next section describes the applications of our methodology to the synthesis of naphthylamines, specifically using the palladium catalysed α-arylation reaction. A discussion of the α-arylation reaction is included as well as our efforts to explore the scope of the reaction. The third section follows our efforts to apply this methodologyy to the synthesis of five benzo[c]phenanthridine alkaloids including the first reported synthesis of maclekarpine B and C. The final section concludes with a discussion of our efforts towards the de novo synthesis of furans bearing a benzylic stereocentre.
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Salem, Hemida Manar Mahfouz. "Identification of antikinetoplastid compounds from Psorothamnus polydenius and P. arborescens." Columbus, Ohio : Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1127103915.
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McCombs, John D. "Studies in marine natural products : Biologically active compounds from the New Zealand algae and invertebrata." Thesis, University of Canterbury. Chemistry, 1989. http://hdl.handle.net/10092/7319.
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In the search for new classes of compounds with antiviral, antitumour or antibacterial activity, a number of benthic marine species were examined.
The extract of Tedania connectens was found to contain three compounds with intense in vitro antiviral and cytotoxic activity (IC₅₀ against P388 murine leukemia cells was 20-40 pg/ml). Examination of the mass spectra of these compounds indicated the presence the known compound tedanolide, together with a deoxy and a chlorinated derivative.
Attempts to convert the antiviral and cytotoxic compound thyrsiferol to thyrsifer-18-one and to the 18-epimer were unsuccessful. However, the ¹H and ¹³C
NMR spectra of thyrsiferyl acetate, including all the pro-r and pro-s proton resonances, were completely assigned using a combination of 2D NMR spectroscopy and molecular mechanics calculations.
Two new dimeric butenolides were isolated from the red alga Delisea elegans, and their structures determined by single X-ray crystallography. The crystal structure of discorhabdin C, a cytotoxic pigment from a sponge of the genus Latrunculia, was determined, as was the crystal structure of the p-bromobenzoyl derivative of the known compound eudistomin K.
Several computer programs were written to assist data analysis. The program
''MassCalc'' was written to free the chemist from the tedious computational tasks usually associated with interpreting mass spectra. A group of five programs were written to simplify the interpretation of the results of molecular mechanics and X-ray crystallography calculations.
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Bhusaunahalli, Vedamurthy Maheswarappa. "Natural polyphenols as lead compounds in the synthesis of antitumor agents and other useful products." Doctoral thesis, Università di Catania, 2012. http://hdl.handle.net/10761/961.
Full textAbstract:
NATURAL POLYPHENOLS AS LEAD COMPOUNDS IN THE SYNTHESIS OF ANTITUMOR AGENTS AND OTHER USEFUL PRODUCTS
Abstract
Some polyphenol dimers, such as lignans, neolignans and stilbenoid lignans, because of their biological properties as well as their structural variety, are an attractive target for chemical synthesis or modification. These polyphenols may be considered lead compounds to obtain products with useful properties, for instance as possible antitumor agents. Thus, this three year research work has been oriented to the synthesis of new dimers, obtained by biomimetic oxidative coupling of natural polyphenols belonging to the stilbenoid and phenylpropanoid families, namely resveratrol or caffeic acid analogues. To this purpose we employed both chemical and enzymatic methods; in particular, metal-mediated reactions were used for the synthesis of nitrogenated lignans with a benxanthene core, whereas stilbenolignans were also obtained with laccase-mediated reactions. During this work, an unexpected enzymatic reaction afforded an hydantoin-related product and this result is also reported herein.
The results of this research are discussed mainly in chapter 2, where three sections are reported:
1) Biomimetic synthesis of stilbenolignans
2) Biomimetic synthesis of benzo[k,l]xanthene lignanamides
3) Enzymatic synthesis of hydantoin-related compounds
In each section, we have reported in detail the synthesis, structural determination, and mechanism of the formation of the products. The final goal of our project was to obtain a library of bioactive compounds to be addressed to biological evaluation with the aim to establish structure-activity relationships for a future optimization of the most promising products. The biological evaluation has been completed for the stilbenolignan group and it is in progress for the other compounds.
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Inuki, Shinsuke. "Total Synthesis of Bioactive Natural Products by Palladium-Catalyzed Domino Cyclization of Allenes and Related Compounds." 京都大学 (Kyoto University), 2011. http://hdl.handle.net/2433/142485.
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Incerti-Pradillos, Celia A. "Asymmetric allylation of carbonyl compounds : kinetic resolution of sec-allylboronates and total synthesis of natural products." Thesis, Loughborough University, 2014. https://dspace.lboro.ac.uk/2134/14991.
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Asymmetric allylation of aldehydes with stoichiometric allylmetal reagents has evolved into an efficient and well established methodology for the synthesis of enantiomerically enriched homoallylic alcohols. The use of enantioenriched secondary allylboronates gives rise to a mixture of E/Z homoallylic alcohols with the opposite configuration at the stereogenic centre (reaction 1). The first part of this thesis presents a novel and conceptually different solution to attain high stereoselectivity in the allylation of aldehydes with secondary allylboronates. The method revolves around an efficient kinetic resolution of chiral racemic allylboronates (reaction 2). Catalysis by a chiral Br??nsted acid ensures a face- and Z-selective allylation of aldehydes. This asymmetric allylation has proved successful over a wide range of aldehydes with different electronic and steric properties. The methodology provides a shortcut to enantio- and diastereomerically enriched homoallylic alcohols finding a wide use in pharmaceutical and fine chemicals development. The second part of the present thesis describes the asymmetric total synthesis of two bioactive metabolites of the Pseudopterogorgiane elisabethae family, (???)-elisabethadione and (???)-erogorgiane. Three key reactions steps to introduce the stereogenic centres in the natural product scaffold include asymmetric allylation, oxy-Cope rearrangement and cationic cyclisation.
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Pokomi, Rostand Fankam. "Selection, synthesis and evaluation of novel drug-like compounds from a library of virtual compounds designed from natural products with antiplasmodial activities." University of the Western Cape, 2020. http://hdl.handle.net/11394/7950.
Full textAbstract:
Magister Pharmaceuticae - MPharmMalaria is an infectious disease which continues to kill more than one million people every year and the African continent accounts for most of the malaria death worldwide. New classes of medicine to combat malaria are urgently needed due to the surge in resistance of the Plasmodium falciparum (the parasite that causes malaria in humans) to existing antimalarial drugs. One approach to circumvent the problem of P. falciparum resistance to antimalarial drugs could be the discovery of novel compounds with unique scaffolds and possibly new mechanisms of action. Natural products (NP) provide a wide diversity of compounds with unique scaffolds, as such, a library of virtual compounds (VC) designed from natural products with antiplasmodial activities (NAA) can be a worthy starting point.
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Essack, Magbubah. "Screening extracts of indigenous South African plants for the presence of anti-cancer compounds." Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_8767_1210844967.
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Early man dabbled with the use of plant extracts to cure ailments. This practice has been passed down from generation to generation and today more than 50% of the world'sdrugs are natural products or derivatives thereof. Scientists have thus established a branch of research called natural product research. This branch of research involves the identification and purification of secondary metabolites with a specific biological activity. The methodology involves the screening of plant products for a specific biological activity, purification of the biologically active natural product by separation technology and structure determination. The biologically active natural products is then further scrutinized to serve as a novel drug or lead compound for the development of a novel drug. This research exploited this research methodology.
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Mabande, Edmund Rufaro. "Antimicrobial discovery from South African marine algae." University of the Western Cape, 2018. http://hdl.handle.net/11394/6592.
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>Magister Scientiae - MScAntimicrobials are chemical compounds that destroy or inhibit the growth of microorganisms. The majority of these antimicrobials are actually natural products or natural product derived with key examples being the pioneer antibiotics penicillin and cephalosporin. Antimicrobials are an extremely important class of therapeutic agents; however, the development of drug resistance and slow pace of new antibiotic discovery is one of the major health issues facing the world today. There is therefore a crucial need to discover and develop new antibacterial agents. In this study, the potential of marine algae as a source of new antibiotics was explored. Crude organic extracts and chromatographic fractions obtained from small-scale extraction of 17 different marine algae were used to prepare a pre-fractionated library that would be tested against several disease causing microorganisms. The activity of the pre-fractionated library and purified compounds was determined against a panel of drug resistant microorganisms namely Acinetobacter baumannii ATCCBAA®-1605™, Enterococcus faecalis ATCC® 51299™, Escherichia coli ATCC® 25922™, Staphylococcus aureus subsp. aureus ATCC® 33591™ and Candida albicans ATCC® 24433™. Finally, cytotoxicity tests of 50 selected library extracts and isolated compounds were done against two cell lines namely MCF-7 (breast cancer) and HEK-293 (kidney embryonic). Based on their antimicrobial activity and interesting chemical profiles, the seaweeds Plocamium sp. and Stypopodium multipartitum were selected for further study. Three new and unusual halogenated monoterpenes (4.16, 4.17 and 4.18) were isolated from Plocamium sp., and an unusual meroditerpenoid (5.8) was isolated from Stypopodium multipartitum. The metabolites were purified using preparative (silica gel) chromatography as well as semipreparative normal phase HPLC. The structures of purified compounds were determined from spectroscopic data, including nuclear magnetic resonance (NMR) spectroscopy. A small library of 153 fractions was generated from collections of South African marine algae. Pre-fractionated crude extracts showed excellent antimicrobial activity against all microbes but particularly against Staphylococcus aureus. The compounds were generally active against the Gram positive bacteria and the yeast. In conclusion, three antimicrobial halogenated monoterpenes and an unusual monoterpene were isolated from a Plocamium sp. and Stypopodium multipartitum respectively. Antimicrobial activity of crude fractions was excellent but that of isolated compounds was not as great as anticipated.
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Botes, Marthinus Gerhardus. "Towards the synthesis of makaluvamine-analogues." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96959.
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Thesis (MSc)--Stellenbosch University, 2015.ENGLISH ABSTRACT: Cancer is one of the leading causes of death in developed countries and rising fast as a cause of death in developing countries. The increase of cancer prevalence in developing countries can be attributed to westernisation trends, with lifestyle cancers such as colorectal and lung cancer being amongst the most commonly reported malignant neoplasms. This means that the development of novel methods of treatment is essential in combatting this disease in the developing world. Combinational chemotherapy is one of the best candidates for treatment, but it is reliant on effective compounds targeting different modes of action. It also means that these compounds should be easily and cheaply available. Makaluvamines have been identified as a class of compounds that may have a novel mode of action on top of being known as topoisomerase II inhibitors. This study attempted to devise a short and concise synthetic strategy, based on reported procedures, to construct makaluvamine C analogues. This involved the introduction of a methyl group to an indole intermediate (7,8-dimethoxy-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline), before oxidation to a quarternized pyrroloiminoquinone (7-methoxy-5-methyl-8-oxo-1,3,4,8- tetrahydropyrrolo[4,3,2-de]quinolin-5-ium chloride). The introduction of this methyl group proved problematic, as the indole substrate proved to be difficult to handle and tended to degrade under reaction conditions. The lack of initial success prompted the deviation from the initial route by quarternizing a quinoline intermediate to form a quinolinium iodide salt (4- (dimethoxymethyl)-6,7-dimethoxy-1-methyl-5-nitroquinolin-1-ium iodide). Upon reduction to give 4-(dimethoxymethyl)-6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroquinolin-5-amine, it was discovered that the subsequent ring-closing reaction to produce 7,8-dimethoxy-5-methyl- 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline was still problematic. The synthesis of the target compounds has not yet been successfully completed, but will still be pursued so these compounds can be evaluated for their anticancer activity and have their mode of action tested.
AFRIKAANSE OPSOMMING: Kanker lewer van die grootste bydrae tot mortaliteit in ontwikkelde lande en is vining aan die toeneem in ontwikkelende lande. Die toename van kanker voorvalle in ontwikkelende lande kan toegedra word aan die verwesteringstendens, met kankers soos kolo-rektale- en long kanker onder die mees algemene kwaadaardige neoplasmsas wat aangemeld word – kankers wat gekoppel word aan leefstyl keuses. Dit beteken dat daar ‘n dringende nood is aan nuwe metodes van behandeling van die siekte in ontwikkelende lande. Kombinasie chemoterapie is een van die beste kandidate vir behandel, sienende dat dit gebruik maak van middels was verskillende aspekte van die siekte uitbuit. Om effektief te wees, moet die antikanker middels goedkoop en maklik beskikbaar te wees. Makaluvamines is geïdentifiseer as ‘n klas van antikanker middele wat moontlik ‘n nuwe metode van inhibisie het, tesame met hul topoïsomerase II inhibisie. Hierdie study het daarom gepoog om ‘n korter en meer bondige sintetiese roete saam te stel, wat gebaseer is op literatuur prosedures, om analoeë van makaluvamine C te produseer. Dit het die aanhegging van ‘n metiel group aan ‘n indool tussenproduk (7,8-dimetoksie-1,3,4,5- tetrahidropirolo[4,3,2-de]kinolien) behels, gevolg deur die oksidasie tot die kwaternêre piroloiminokwinoon (7-metoksie-5-metiel-8-oxo-1,3,4,8-tetrahidropirolo[4,3,2-de]kinolin-5-ium chloried). Om hierdie metiel groep aan te voeg was, nietemin, problematies, aangesien die indool produk moeilik was om te hanteer sienende dat dit onder reaksie toestande gedegradeer het. Die aanvanklike onsuksesvolle pogings het daartoe gelei dat die sintetiese roete herdink was en is aangepas om eerder gebruik te maak van ‘n kinolinium jodied sout (4-(dimetoksiemetiel)-6,7-dimetoksie-1-metiel-5-nitrokinolin-1-ium jodied). Die reduksie van hierdie sout en agtereenvolgende annulasie reaksie om 7,8-dimetoksie-5-metiel-1,3,4,5- tetrahidropirolo[4,3,2-de]kinolien te vorm was egter steeds problematies. Die sintese van die beoogde produkte was tot dusver nog nie suksesvol nie, maar sal egter steeds aangedurf word om hulle ten einde suksesvol te sintetiseer en dan te stuur om hulle biologiese eienskappe te toets. Dit sluit hulle antikanker aktiwiteit in asook hul metode van inhibisie.
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Rashatasakhon, Paitoon. "Vinyloxocarbenium ions and cyclopentenyl oxyallyl, zwitterions in 4+3 cyloadddition reactions /." free to MU campus, to others for purchase, 2002. http://wwwlib.umi.com/cr/mo/fullcit?p3052211.
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Akintunde, Olaitan G. "Production of an Antibiotic-like Activity by Streptomyces sp. COUK1 under Different Growth Conditions." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2412.
Full textAbstract:
Streptomyces are known to produce a large variety of antibiotics and other bioactive compounds with remarkable industrial importance. Streptomyces sp. COUK1 was found as a contaminant on a plate in which Rhodococcus erythropolis was used as a test strain in a disk diffusion assay and produced a zone of inhibition against the cultured R. erythropolis. The identity of the contaminant was confirmed as Streptomyces through 16S rRNA sequencing. This Streptomyces produces a strong inhibitory compound in different growth media. A culture extract from inorganic salts starch agar was found to be very active; producing a large zone of inhibition against several Gram positive and Gram negative test strains. The active molecules in this extract have been detected via TLC and bioautography. The difference in the antibacterial activity and chromatographic properties of extracts recovered from different growth media suggests that this Streptomyces strain could produce more than one type of inhibitory compound.
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Patil, Dadasaheb V. "Intramolecular cyclization strategies for synthesizing medium-ring polycycles and the total synthesis of natural products." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/50118.
Full textAbstract:
Carbo- and heterocyclic compounds are of great interest to chemists. Intramolecular cyclization strategies of donor-acceptor (D-A) cyclopropanes and alkylidene malonate monoamides have excellent potential for synthesis as they offer easy access to structurally-diverse compounds. The work described in this thesis accesses the scope of the In(OTf)3-catalyzed cyclization reaction of cyclopropanes and alkylidene malonate monoamides. In(OTf)3-catalyzed reactions of alkenyl and heteroaryl cyclopropyl ketones were examined in the synthesis of functionalized cyclohexenone-based derivatives (Chapter 2). Subsequent efforts to utilize a tandem cyclopropane ring-opening/Friedel-Crafts alkylation sequence of methyl 1-(1H-indolecarbonyl)-1-cyclopropanecarboxylates to prepare functionalized hydropyrido[1,2-a]indole-6(7H)-ones is discussed in Chapter 3. The extension of this tandem protocol towards the total synthesis of (±)-deethyleburnamonine is the subject of Chapter 6. Intramolecular Friedel-Crafts alkylation of N-indolyl alkylidene malonate monoamides was also examined. An In(OTf)3-catalyzed cyclization of substituted methyl 2-(1H-indole-1-carbonyl) acrylates afforded a series of 1H-pyrrolo[1,2-a]indole-3(2H)-ones (Chapter 4), whereas substrates with the indole 2-position blocked provided access to substituted 4H-pyrrolo[3,2,1-ij]quinolin-4-ones (Chapter 5).
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PAN, CHENGQIAN. "Discovery of Novel Bioactive Compounds from a Rare Actinomycete Amycolatopsis sp. 26-4." Kyoto University, 2020. http://hdl.handle.net/2433/259019.
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Eaton, Alexander Lee. "Isolation and Synthesis of Bioactive Compounds from Plants." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/64367.
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As a part of a continuing search for bioactive compounds with the International Cooperative Biodiversity Group (ICBG), and in collaboration with the Natural Products Discovery Institute of the Institute for Hepatitis and Virus Research (IHVR), twelve plant extracts were investigated for their antiproliferative activity against the A2780 cell line, three plant extracts were investigated for their antimalarial activity against Plasmodium falciparum, and three plant extracts were investigated for their anti-inflammatory activity (PPAR-y inhibition). Bioassay-guided fractionation of extracts led to the identification of four new antiproliferative compounds (2.1-2.3, 3.1), five new anti-inflammatory compounds (6.4a, 6.5a-b, 6.6a, 6.6c), and twenty-eight known compounds from eight of the extracts. In addition, mallotojaponin C, an antimalarial natural product, and derivatives were synthesized and investigated for their antimalarial activity.Ph. D.
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Kaduskar, R. D. "TOTAL SYNTHESIS AND ANTIMICROBIAL ACTIVITY EVALUATION OF NATURAL PRODUCTS AND THEIR ANALOGUES." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/478522.
Full textAbstract:
The need to develop new antimicrobials remains a major driving force as microorganisms continue to develop resistance against existing antibiotics.
Natural products are large reservoirs of new biologically active substances and most of the currently used antimicrobials have been developed from naturally occurring lead compounds. Aim of the PhD work was the study of new naturally derived antimicrobial compounds and the development of synthetic sequences which might, in principle, have value in the preparation of the natural products themselves as well as in synthesizing various analogues. Among a number of possible candidates we have selected three natural products, Leopolic acid A, Promysalin and Resormicyn.
During the PhD period the synthesis of these natural products has been carried out, and the biological activity of the compounds has been evaluated. Key steps of the synthetic approach to Promysalin encompass an organocatalytic asymmetric α-hydroxylation of carbonyl compounds employed to fabricate the myristamide framework, and Superhydride® mediated reductive elimination of lactam to obtain the salicyldehydroproline fragment. Crucial steps for the leopolic acid synthetic strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. Finally, the key steps in resormicyn synthetic approach include the late stage stereospecific dehydration of alcohol to install the Z-olefin and palladium catalyzed one-pot deprotection of allyl and alloc groups.
The straightforward and modular nature of the developed syntheses has given easy access to the preparation of structurally related analogues and the biological activity of the compounds has been evaluated. Preliminary SAR have emerged for promysalin and leopolic acid.
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Chamyuang, Sunita. "Application of selective methods in the search for new bioactive natural products from fungi." Thesis, University of Canterbury. School of biological Science, 2010. http://hdl.handle.net/10092/3702.
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The work undertaken explored the potential for discovery of new bioactive metabolites from soil fungi. The research developed selective mycological isolation techniques and maximised metabolite production from active selected fungi by application of the OSMAC approach and concept of hormesis. Novel active compounds were discovered and many other known compounds characterised.
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彭向榮 and Heung-wing Pang. "Studies toward the total synthesis of biologically active cyclodepsipeptides." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31227752.
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Calder, Ewen D. D. "The development of one-pot multi-reaction processes for the synthesis of natural products and biologically active compounds." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6667/.
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This thesis is divided into four chapters in which one-pot processes have been developed and utilised for the synthesis of biologically active compounds. The work in the first chapter outlines the 13-step total synthesis of D -ribo- and L - arabino-phytosphingosine from D -ribose. This process employed a microwave promoted Overman rearrangement of an allylic trichloroacetimidate to install the amine functionality. In the second and third chapters, the development of a one-pot, two-step Overman/ring closing metathesis process is detailed. The synthesis of three different classes of starting material is also shown. This one-pot process was used as the key step in the synthesis of four oxybenzo[c]phenanthridine natural products and the partial synthesis of an ACAT inhibitor. The potential for further functionalisation of the products by oxidation and reduction was also explored. In the final chapter, a one-pot allylboration/Heck process for the synthesis of indan-1-ols is described. Optimisation and an investigation of the scope of the process are also presented. The process was then altered to allow the use of a chiral phosphoric acid catalyst for the asymmetric synthesis of these compounds.
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Chen, Jhong-Min. "Chemoenzymatic Studies to Enhance the Chemical Space of Natural Products." UKnowledge, 2015. http://uknowledge.uky.edu/pharmacy_etds/48.
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Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.
Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most challenging part was to modify the sugar moiety. In order to solve this problem, PV was used as an alternative lead-structure for modification because its sugar moiety offered the possibility of enzymatic O-methylation. We produced four PV derivatives with different methylation patterns for cytotoxicity assays and provided important structure-activity-relationship information.
Mithramycin (MTM) is the most prominent member of the aureolic acid type anticancer agents. Previous work in our laboratory generated three MTM analogues, MTM SA, MTM SK, and MTM SDK by inactivating the mtmW gene. We developed new MTM analogues by coupling many natural and unnatural amino acids to the C-3 side chain of MTM SA via chemical semi-synthesis and successfully made some compounds with both improved bioactivity and in vivo tolerance than MTM. Some of them were consequently identified as promising lead-structures against Ewing’s sarcoma.
The potential of selectively generating novel MTM analogues led us to focus on a key enzyme in the biosynthetic pathway of mithramycin, MtmC. This protein is a bifunctional enzyme involved in the biosynthesis of TDP-D-olivose and TDP-D-mycarose. We clarified its enzymatic mechanisms by X-ray diffraction of several crystal complexes of MtmC with its biologically relevant ligands. Two more important post-PKS tailoring enzymes involved in the biosynthesis of the MTM side chains, MtmW and MtmGIV, are currently under investigation. This would not only give us insight into this biosynthetic pathway but also pave the way to develop potentially useful MTM analogues by engineered enzymes.
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Salinas-Roca, Blanca. "Preserving natural attributes of mango products by non-thermal technologies." Doctoral thesis, Universitat de Lleida, 2017. http://hdl.handle.net/10803/405840.
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Els consumidors demanden nous productes a base de fruites -com els a punt per menjar-, segurs,
saludables i amb propietats similars als naturals. L’objecte d’estudi d’aquesta tesi doctoral fou
avaluar l’impacte de tractaments no tèrmics en propietats de qualitat de diversos productes de
mango: tallat, suc i puré.
Per una banda, l’efecte de diferents recobriments a base de polisacàrids, alginat (AL), quitosan
(CH), pectina (PE) i carboximetilcel·lulosa (CMC), es va avaluar en la conservació de la qualitat
del mango tallat. També, l’efecte dels polsos de llum (PL) combinats amb el recobriment AL i la
immersió en àcid màlic (MA) va permetre allargar la conservació dels atributs naturals durant 14
dies. D’altra banda, es va estudiar la influència dels polsos elèctrics d’alta intensitat de camp
HIPEF a 35 kV/cm, 4 μs- pols bipolar, 200 Hz i 50- 2000 μs en la reducció de població de
Listeria innòcua, l’activitat enzimàtica, les propietats sensorials així com el contingut de
bioactius. En aquest sentit el contingut de fenols en el suc tractat per HIPEF (1800 μs) va millorar
després de 59 dies. Finalment, es va estudiar l’impacte del tractament d’alta pressió hidrostàtica
(HHP) (400, 450, 500 MPa durant 0 a 16 min a 34 o 59°C) en les propietats fisicoquímiques i
enzimàtiques, com també en el contingut de compostos bioactius del puré de mango.
Aquesta investigació mostra la viabilitat de la conservació dels derivats de fruita mitjançant
tecnologies no tèrmiques.Consumers are currently demanding safe, healthy and novel fruit products, such as ready-to-eat, with natural attributes. Therefore, the aim of the present doctoral thesis was to assess the impact of non-thermal treatments on quality properties of various mango products: fresh-cut, juice and puree. On one hand, the effect of different polysaccharide-based coatings, alginate (AL), chitosan (CH), pectin (PE) and carboxymethylcellulose (CMC) was evaluated on the quality preservation of fresh-cut mango. Also in fresh-cut mango, the effect of pulsed light (PL) combined with AL coating and malic acid (MA) dipping extended preservation of natural attributes throughout 14 days. On the other hand, the influence of high intensity pulsed electric fields (HIPEF) at 35 kV/cm, 4 μs- bipolar pulses, 200 Hz and 50-2000 μs in mango juice was studied in the reduction of Listeria innocua population, enzymatic activities, physicochemical and sensorial attributes as well as the content of bioactive compounds. In this sense, phenolic content in mango juice treated with HIPEF (1800 μs) was improved after 59 days. Finally, the impact of high hydrostatic pressure (HHP) treatments (400, 450, 500 MPa for 0 to 16 min at 34 or 59°C) on physicochemical, enzymatic properties and bioactive compounds of mango puree was observed. This research reveals the feasibility of preserving fruit products by non-thermal technologies.
Los consumidores piden nuevos productos a base de frutas, como los listos para el consumo, seguros, saludables y con propiedades similares a los naturales. Por lo tanto, el objeto de estudio de la presente tesis doctoral fue evaluar el impacto de tratamientos no térmicos en la calidad de diversos productos de mango: cortado, zumo y puré. Por un lado, el efecto de diferentes recubrimientos a base de polisacáridos, alginato (AL), quitosano (CH), pectina (PE) y carboximetilcelulosa (CMC) se evaluó en la conservación de la calidad del mango cortado. También, el efecto de los pulsos de luz (PL) combinado con el recubrimiento AL y la inmersión en ácido málico (MA) permitió alargar la conservación de los atributos naturales durante 14 días. Por otro lado, se estudió en el zumo de mango la influencia de los pulsos eléctricos de alta intensidad de campo (HIPEF) a 35 kV/cm, 4 μs- pulso bipolar, 200 Hz y 50- 2000 μs en la reducción de población de Listeria innocua, la actividad enzimática, las propiedades sensoriales así como el contenido de bioactivos. En este sentido el contenido de fenoles en el zumo de mango tratado por HIPEF (1800 μs) mejoró después de 59 días. Finalmente, el impacto del tratamiento por alta presión hidrostática (HHP) (400, 450, 500 MPa de 0 a 16 min a 34 o 59°C) se observó en las propiedades fisicoquímicas y enzimáticas y en el contenido de compuestos bioactivos en el puré de mango. La presente investigación muestra la viabilidad de la conservación de derivados de frutas mediante tecnologías no térmicas.
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Mazraati, Tajabadi Fatemeh. "Identification of 3D Scaffolds Embedded in Natural Products and Synthesis of Focused Libraries." Thesis, Griffith University, 2017. http://hdl.handle.net/10072/365575.
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The ever-increasing demand for new drugs drives the need to explore new areas of biologically-relevant chemical space. Drug targets, largely the active sites of proteins, have three-dimensional shape. However, chiefly for reasons of synthetic tractability, the screening libraries that are extensively used for high throughput screening (HTS) drug discovery are mostly composed of flat aromatic and heteroaromatic compounds.1 This has resulted in a trend towards flatness in drug candidates, limiting the possibilities in the navigation of three-dimensional biological space. A variety of approaches, such as diversity-oriented synthesis (DOS),2, 3 target-oriented synthesis (TOS),2, 4 function-oriented synthesis (FOS),5 and biology-oriented synthesis (BIOS)6, 7 have emerged to address this issue. Natural products are a source of therapeutically useful compounds with high success rates in drug discovery.8 They tend to be highly saturated, and therefore non-flat, molecules with chiral centres. These features of natural products arise from interaction with the active sites of proteins involved in biosynthetic pathways. Inspired by natural products, we sought to identify three-dimensional (3D) molecular scaffolds embedded in natural products with the aim of producing focused synthetic libraries that explore new biological profiles.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
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Akram, Zain. "Yeast-based approaches to identify and characterise the mode-of-action of bioactive natural products with a focus on the anthracyclines." Thesis, Griffith University, 2022. http://hdl.handle.net/10072/420601.
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Natural compounds have been commercially used in pharmaceutical industry due to their therapeutic nature. Herein, natural compounds are screened that modulate various biological processes that are known to be conserved from yeast to human and to be associated with human diseases such as cancers and viral infections. Baker’s yeast Saccharomyces cerevisiae is a eukaryotic model in the pharmaceutical industry and its use allows genome-wide recognition of potential targets of natural compounds.
Cancer is one of the leading causes of death worldwide with the number of diagnosed cases of this disease escalating. Chemotherapy remains the number one treatment option, especially in developing countries where other forms of treatment remain costly. The anthracyclines (natural compounds) are chemotherapeutic agents that have been in use for the last forty years and that are effective in treating various solid tumours as well as haematological malignancies. Various modes of action have been suggested for these agents; however, it remains unclear as to how these agents really exert their cytotoxic effects on cells. Anthracyclines can cause severe adverse effects such as cardiotoxicity as well as myelosuppression, and these are the major limitations of these drugs. To solve these problems, the controversy regarding their mechanism of action needs to be addressed. For this reason, here the focus is on the analysis of molecular mechanisms responsible for anthracycline cytotoxicity and the identity of the intracellular compartments that anthracyclines localise to in a mammalian cell line and relate the findings to those controversies found in the literature. In addition, natural compound-based potential anti-viral compounds that may inhibit cellular vacuolar protein sorting-4 (Vps4p) ATPase activity and in parallel block viral budding from the cellular membrane were also investigated.
Natural compounds have been largely excluded from characterisation via high-throughput profiling strategies due to their limited abundance. A previous investigation used high-throughput yeast chemical genomic (CG) interaction profiling to permit the identification of putative cellular targets for the naturally-derived anthracycline-related compound epsilon rhodomycinone (ε-Rh) and the related synthetic compound 1,6,11-trihydrotetracene-5,12-dione (D11) in yeast. A set of 54 putative targets were identified using the wild-type yeast strain BY4741 and genome-wide set of congenic gene knockout mutants harbouring complete deletions of individual nonessential genes. Here, the focus is on the hypersensitivity of a specific subset of those mutant strains that each harbour a complete deletion of a different gene. Examining these hypersensitive strains can identify the possible targets whose altered activity is the molecular mechanism for anthracyclines. The results from this study identify and confirm the hypersensitivity of the BY4741 sod1Δ gene deletion mutant to the compound ε-Rh, D11 and clinically used anthracyclines (doxorubicin and daunorubicin). The identification of the sod1Δ gene supports the validity of this yeast-based approach for identifying cellular target(s) of these drugs, because anthracyclines have been reported to damage mammalian cells by generating reactive oxygen species such as superoxide and the SOD1 gene encodes superoxide dismutase, which is an enzyme responsible for breakdown of superoxide. Therefore, yeast haploid gene deletion mutants in which the gene encoding Sod1p is deleted (sod1Δ) display hypersensitivity to these drugs and this result agrees with expectations.
A cultured mammalian cell line was also used to identify cellular compartments in which internalised natural and clinically used anthracyclines accumulate. The results from this study demonstrate that both ε-Rh and clinically used anthracyclines (doxorubicin and daunorubicin) localise within the nucleus. This study identifies that the main mode of action for these anthracyclines is in the nucleus with no functional interaction with plasma membrane or any other cellular compartment. These findings are in accordance with the previous collected yeast chemical genomics analysis data that showed radiation sensitive RAD genes (localised within nucleus) as cellular targets of these anthracyclines. Moreover, the disruption of SOD1 gene generates reactive oxygen-species that lead to the DNA double-strand breaks within the nucleus. Therefore, ε-Rh mode of action can be considered as a potential anti-cancer, but its toxicity needs to be tested.
In parallel, the screening of a natural extracts (335 marine compounds) library using yeast as a model organism was completed with the aim of identifying a novel Vps4p inhibitor with potential application as an anti-viral compound. This exhaustive screening was not able to provide any positive hit; however, this study found that the commercially available DBeQ (an inhibitor of p96) is also an inhibitor of Vps4p in S. cerevisiae but did not abolish the Vps4p physical interaction with the associated protein Vps2p. Overall, the findings presented in this thesis has advanced the knowledge regarding the application of yeast for the screening of natural products to characterise the mode of action of bioactive natural products on all eukaryotic cells. This knowledge can then be used for the design of novel compound for cancer and/or enveloped virus infections.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Pharmacy & Med Sci
Griffith Health
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Schäfer, Christian. "Reactivity of acetylenic ω-keto-esters towards transition metal complexes : synthesis of polycyclic motives of natural products." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAF006/document.
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Les travaux décrits dans ce mémoire ont pour objet l’étude de la réactivité des ω-céto-esters acétyléniques vis-à-vis des métaux de transition. Lorsque ces composés sont traités avec une mélange Ti(OiPr)4/iPrMgBr, la formation d’alcools allyliques bicycliques est observée avec une totale diastéréosélectivité par rapport à la jonction de cycle (cis) et une configuration (E) pour la double liaison. Il a été montré que ces produits peuvent être transformés en lactone α,β-insaturé, sous-structures de produits naturels. La cycloisomérisation d’alcynyl cétones catalysées par des sels d’Ag(I) conduit à la formation de composés spiraniques. En piégeant l’intermédiaire réactionnel, la synthèse des composés vinyl-iodés correspondants a été réalisée. Si la réaction de cycloisomérisation est effectuée avec des ω-céto-esters acétyléniques, des ester α,β-insaturés sont isolés. Les produits obtenus ont ensuite été utilisés comme substrats pour la formation de systèmes tricycliques 6-5-5 et 6-6-5. Ces enchaînements de cycles sont présents dans le squelette carboné d’une grande variété de produits naturels. Les travaux décrits dans ce mémoire ont pour objet l’étude de la réactivité des ω-céto-esters acétyléniques vis-à-vis des métaux de transition. Lorsque ces composés sont traités avec une mélange Ti(OiPr)4/iPrMgBr, la formation d’alcools allyliques bicycliques est observée avec une totale diastéréosélectivité par rapport à la jonction de cycle (cis) et une configuration (E) pour la double liaison. Il a été montré que ces produits peuvent être transformés en lactone α,β-insaturé, sous-structures de produits naturels. La cycloisomérisation d’alcynyl cétones catalysées par des sels d’Ag(I) conduit à la formation de composés spiraniques. En piégeant l’intermédiaire réactionnel, la synthèse des composés vinyl-iodés correspondants a été réalisée. Si la réaction de cycloisomérisation est effectuée avec des ω-céto-esters acétyléniques, des ester α,β-insaturés sont isolés. Les produits obtenus ont ensuite été utilisés comme substrats pour la formation de systèmes tricycliques 6-5-5 et 6-6-5. Ces enchaînements de cycles sont présents dans le squelette carboné d’une grande variété de produits naturelsIn this work, the reactivity of acetylenic ω-ketoesters towards different metal complexes was investigated. When acetylenic ω-ketoesters are submitted to Ti(OiPr)4/iPrMgBr, the formation of fused bicyclic γ-hydroxy-α,β-unsaturated esters was observed. The products were obtained with absolute selectivity in regard to the ring junction formed (cis) and the configuration of the double bond (E) and could be transformed into the corresponding α,β-unsaturated lactones, substructures of various natural products. When ω-ketoalkynes are used in Ag(I)-catalyzed cycloisomerization reactions, the formation of spirocyclic compounds was observed. By taking advantage of the reaction intermediates of this reaction, it was possible to isolate the corresponding spirocyclic alkenyl iodides. Performing cycloisomerization reactions with acetylenic ω-ketoesters, spirocyclic α,β-unsaturated esters are formed. We could show that these products are valuable substrates for the formation of 6-5-5- and 6-6-5-fused tricyclic systems which represent the skeleton of a large group of natural products
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Segopa, Ellen Kelebogile. "Marine bacteria as a potential source for novel antimicrobial compounds." University of the Western Cape, 2021. http://hdl.handle.net/11394/7918.
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>Magister Scientiae - MScThe high rate of rediscovery of known compounds has led to a decline in the discovery of novel natural products. The high biodiversity of organisms growing in extreme conditions such as oceans has led to the increased interest by researchers for their use as a source of novel natural products. Marine bacteria are known for their extensive biosynthetic capacity to produce diverse natural products, which are suitable for various biotechnology applications such as in agriculture, for treatment of fungal plant pathogens, and as antibiotics, for treatment of bacterial infections. This study aimed at discovering novel secondary metabolites from marine bacteria previously associated with novel marine invertebrate species endemic to the South African coast. The methodologies used in this study included a bioassay guided fractionation coupled to genome sequencing and mining. For the bioassay guided fractionation approach, the study first focused on screening marine bacteria for antimicrobial activity when cultured on 4 different media, against fungal strains previously shown to be virulent olive trunk pathogens. In parallel, the bacterial isolates with the most inhibitory activity against the fungal pathogens were also screened for antimicrobial activity against 4 indicator strains including Gram-negative Escherichia coli 1699 (E. coli), Pseudomonas putida, and Gram-positive Staphylococcus epidermidis ATCC14990, and Bacillus cereus ATCC10702. One of the marine bacterial isolates, PE6-126, showed diverse antimicrobial activity including antibacterial and antifungal activity against the tested strains. The genome sequencing data revealed that this isolate was B. cereus based on the average nucleotide identity (ANI) (>99%) to reference strains. antiSMASH analysis of the genome revealed nine predicted secondary metabolite clusters including bacteriocins (2), non-ribosomal peptide synthetase (NRPS) (2), siderophore (1), sactipeptide (1), betalactone (1), linear azol(in)e-containing peptides (LAP) - bacteriocin (1) and a terpene (1). Some of these pathways had low to no sequence similarity to known pathways, indicating the potential of these pathways to produce novel compounds. One of the pathways showed very high sequence similarity to the thuricin CD pathway in Bacillus thuringiensis. Considering that thuricin CD has been reported to have antimicrobial activity against B. cereus (ATCC1072), it was hypothesised that it could also be produced by PE6-126. However, the antimicrobial extract from PE6-126 was tested for sensitivity to proteinase K and heat treatment, which thuricin CD is known to be sensitive to. The results revealed that the antimicrobial activity was not lost after treatment, implying that a different metabolite could be responsible for the anti-B. cereusactivity. In addition, PE6-126 initially displayed antimicrobial activity against a multi-drug resistant E. coli 1699, suggesting some of the antimicrobial compound/(s) produced by this strain could potentially be novel. The bioassay-guided fractionation approach coupled to Liquid Chromatography Mass Spectrometry (LC-MS) did not lead to identification of the antimicrobial compound/(s), therefore it remains a question whether the secondary metabolite pathways predicted by antiSMASH lead to the production of the active compound/(s).The results from this study showed that even well studied species have the potential to synthesize as yet undescribed compounds, based on the novelty of some of the pathways. This study highlights the importance of employing a genome-guided approach in drug discovery, as there may be many novel compounds to discover from biosynthetic pathways that have not yet been characterised. Further research is needed to identify the antimicrobial compound/(s) produced by PE6-126.
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Löbermann, Florian Wolfgang [Verfasser], and Dirk [Akademischer Betreuer] Trauner. "Contributions to the chemistry of polyhydroxylated aromatic compounds : methodology, natural products and materials science / Florian Wolfgang Löbermann. Betreuer: Dirk Trauner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1051258987/34.
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Bahar, Mark. "Protoberberine-type Alkaloids as Lead Compounds for the Treatment of African Sleeping Sickness, Leishmaniasis, and Malaria." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1330974078.
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Mori, Ana Luiza Pereira Moreira. "Própolis - identificação de flavonóides e ácidos aromáticos em tintura. Estimativa de FPS de extrato mole em base cosmética." Universidade de São Paulo, 1997. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-10022015-155633/.
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A realização deste trabalho objetivou a avaliação quantitativa da absorção da radiação UVB (290-320 nm) em oito amostras de própolis, incorporadas em base cosmética apropriada, sob a forma de extrato mole, originárias de diversas regiões com diferentes origens botânicas sendo duas de Minas Gerais, três de São Paulo, uma de Santa Catarina, uma do Rio Grande do Sul e outra da Pensilvânia - EUA. A estimativa de absorção foi feita através de método espectrofotométrico com medidas de absorbâncias na faixa entre 290 a 320 nm, tomadas de 5 em 5 nm. Cada medida de absorbância foi relacionada à intensidade e ao efeito eritemogênico da radiação em seu respectivo comprimento de onda. Os resultados tiveram como parâmetro o padrão de referência salicilato de homomentila, aprovado pela FDA para determinação de FPS in vivo. Foi obtido um perfil cromatográfico através de cromatografia em camada delgada para avaliação qualitativa de nossas amostras em relação a alguns flavonóides e ácidos aromáticos, o que nos permitiu constatar a presença de ácido cafeico em todas as amostras analisadas. Foram dosados flavonóides totais por método colorimétrico com cloreto de alumínio, expressos em crisina a 330 nm. Foi feita a comparação entre os resultados de FPS e flavonóides totais e observamos proporcionalidade direta entre a maioria das amostras, o que confirma a ação de absorção de radiação ultra-violeta por flavonóides colhidos pelas abelhas em plantas.The aim of this work was to evaluate quantitatively the UVB absorption (290-320 nm) of propolis, contained in eight cosmetic samples as soft extract, from different botanical origins and several regions, such as Minas Gerais, São Paulo, Santa Catarina, Rio Grande do Sul and Pennsylvania (USA). A spectrophotometric method using absorbance measurements in a range of 290-320 nm, taken at 5 nm intervals, was used to asses the absorbance. Each absorbance measurement was related to both intensity and erythemal effect of the radiation at its respective wavelength. Homosalate, which is approved by the FDA as reference standard, was used for the determination of SPF in vivo. Chromatograms of the samples were obtained by thin-layer chromatography to evaluate the presence of some flavonoids and aromatic acids in the samples. This technique allowed the detection of caffeic acid in all the analyzed samples. The total flavonoids content was assayed by the colorimetric method using aluminum chloride, and the results were expressed in chrysin at 330 nm. A comparison between the SPF results and the total flavonoids contend was done and a direct relationship between most of the samples was observed, confirming the absorbing ultraviolet radiation property of the flavonoids collected by bees.
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Abdelhamid, Dalia. "Natural Products as Lead Compounds for Drug Development. Part I: Synthesis and Biological Activity of a Structurally Diverse Library of Curcumin Analogues. Part II: Synthesis of Novel Sterol Natural Products and Related Analogues as Antileishmanial Ag." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1299685922.
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