Дисертації з теми "Inhibitor Activity"
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Stott, Holly Rosannah. "MMP-12 activity during vascular remodelling." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/23609.
Повний текст джерелаEckelman, Brendan P. "The regulation of caspase activity by the inhibitor of apoptosis proteins." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC IP addresses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3288846.
Повний текст джерелаTitle from first page of PDF file (viewed June 2, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 188-214).
Gora, Kasia G. (Kasia Gabriela). "SciP : a novel inhibitor of CtrA transcriptional activity in Caulobacter crescentus." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68426.
Повний текст джерелаCataloged from PDF version of thesis. "August 8, 2011."
Includes bibliographical references.
Cells must sense changes in their environment and respond appropriately in order to survive. A common survival strategy is for cells to translate an environmental signal into the activity of a transcription factor they effects a change in gene expression. In this way, cells can express a gene just-in-time for its biological function. In addition, cells can coordinate the activity of many transcription factors to construct genetic regulatory networks that integrate many inputs to control complex cellular behaviors. In this thesis, I use the model system Caulobacter crescentus to examine the regulation of CtrA, the essential transcription factor at the core of the Caulobacter cell cycle regulatory network. CtrA regulates the activity of approximately 100 cell cycle genes many of which are critical for cell cycle progression. CtrA activity is regulated at the level of abundance, post-transcriptional modification, and here I show that CtrA is also regulated by a novel protein-protein interaction. I identify SciP, a GI specific inhibitor of CtrA transcriptional activity and show that SciP forms a complex with CtrA at CtrA dependent promoters. The SciP/CtrA interaction likely prevents CtrA from recruiting RNA polymerase thereby blocking the activation of transcription. In addition, I show that SciP is restricted to G1 by regulated proteolysis. I identify the Lon as the SciP protease and show that Lon is required for SciP proteolysis in vivo and that E. coli Lon degrades SciP in vitro. Finally I engineer a stable allele of sciP and show SciP proteolysis is critical for proper cell cycle progression.
by Kasia G. Gora.
Ph.D.
Al-Yousuf, Karamallah. "Investigating the anti-melanoma activity of combinatorial paclitaxel and MEK inhibitor." Thesis, University of Dundee, 2018. https://discovery.dundee.ac.uk/en/studentTheses/1be821d2-2436-4c31-8485-e62b86d6d33b.
Повний текст джерелаSancho, Elena. "Conformation and activity of plasminogen activator inhibitor type 1 (PAI-1)." Thesis, University of Aberdeen, 1994. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU552562.
Повний текст джерелаGrundy, Martin. "Activity of the aurora kinase B inhibitor AZD1152 in acute myeloid leukaemia." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12758/.
Повний текст джерелаSampathkumar, Yamuna. "Thermal processing effects on total phenolic content, antioxidant activity, trypsin inhibitor activity and in-vitro protein digestibility of lentils." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107918.
Повний текст джерелаLe prétraitment thermique de lentilles avant de les moudre en farine peut faciliter son utilisation dans la préparation de produits à valeur ajoutée. Cette étude porte sur l'évaluation des effets des prétraitments thermiques par chauffage par torréfaction(CT), par chauffage par microondes (CM), ou par l'eau bouillante (EB), sur la teneur en composés phénoliques totaux (CPT), sur l'activité anti-oxydante totale (AAOT), sur les teneurs en inhibiteur de trypsine, et sur la digestibilité in-vitro des protéines (DIVP). Les essais ont été faits sur des farines obtenues à partir de lentilles rouges décortiquées et de lentilles vertes non decortiquées après l'application des prétraitment thermiques. Les deux varieties de lentilles ont été prétraitées selon des combinaisons déterminées de températures et de durées de traitment. Les teneurs en CPT et l'AAOT ont été évaluées par spectrophotométrie à 760 nm en utilisant la méthode de Folin-Ciocalteu et la méthode DPPH (1, 1- diphényl-2-picrylhydrazyle) de piégeage des radicaux libres. Les résultats ont démontré des différences significatives entre les deux types de lentilles étudiées. Le prétraitement CM (5 min) a conduit à une augumentation significative (P≤0.05) de la teneur en CPT dans les échantillons de farine de lentilles vertes [8.85 mg GAE/g de poids sec (ps) lorsque comparé aux échantillons de farine de lentilles vertes non-traitées [7.5 JEU mg/g ps]. Une tendance similaire a été observée auprés des farines de lentilles vertes torréfiées au four pendant 20 min. L'AAOT des farines de lentilles vertes non-traitées était d'environ 86% et elle était supérieure à celle obtenue à partir de lentilles rouges non-traitées. Les teneurs en CPT observées dans les échantillons traités soit par CT soit par CM étaient plus élevées que celles des échantillons non traitées et peuvent refléter des réductions en AAOT obetnues. Les teneurs en CPT et en AAOT des échantillons obtenues à la suite du prétraitment EB étainet nettement inférieures et peut être attributées à plusieurs facteurs dans la matrice. Bien que les lentilles soit riches en protéines, plusiers facteurs limitent leurs utilisation pour la consommation humaine. Ces principaux facteurs sont : la présence de composants antinutritionnels, le temps nécessaire à la préparation, les saveurs désagréables, et la digestibilité réduites des protéines. On peut réduire l'impacte des facteurs antinutritionnels comme les inhibiteurs de la trypsine par des traitements thermiques. Les résultats ont demontré que l'utilisation du pretraitment CM permettait de réduire significativement (P≤0.05) l'activité des inhibiteurs de trypsine lorsque comparés aux prétraitments CT et EB. Il a aussi été démontré que l'augmentation de la dureé des prétraitments thermiques par CT ou par EB permettait d'accroitre la DIVP. Dans tous les cas étudiés, l'application d'un prétraitment thermique sur les lentilles a permis d'améliorer la DIVP.Mots clés : Lentilles vertes, lentilles rouges, farines, traitements thermiques, composés phénoliques totaux (CPT), activité anti-oxydante totale (AAOT), digestibilité in-vitro des protéines (DIVP), équivalent en acide gallique, chauffage par torréfaction (CT), chauffage par microondes (CM), chauffage par trempage dans l'eau bouillante (EB).
Mendis, Mihiri Marini. "Variability in Arabinoxylan, Xylanase Activity and Xylanase Inhibitor Levels in Hard Spring Wheat." Thesis, North Dakota State University, 2012. https://hdl.handle.net/10365/26806.
Повний текст джерелаNational Science Foundation Grant (# HRD-0811239) to the NDSU Advance FORWARD program
North Dakota Wheat Commission
Zwahlen, Hugo. "Effects of low-dose "Factor VIII Inhibitor Bypassing Activity (FEIBA)" in resistant heamophilia /." [S.l : s.n.], 1986. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Повний текст джерелаRen, Zhongyuan. "Small molecules regulated bone resorption and enzyme activity in osseous cells." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10291/document.
Повний текст джерелаCathepsin K is among the most potent mammalian collagenase, capable of cleaving the triple helix in type-I collagen. We developed a series of azanitriles (CKI-8 and CKI-13) which are inhibitors of cathepsin K. CKI-8 (an isomer of CKI-13) and CKI-13 did not induce significant toxicity on osteoblasts Saos-2 and RAW 264.7 cells up to 1000 nM, while they were not toxic on mature osteoclasts up to 100 nM. Commercial E64 inhibitor was not toxic in primary osteoclast cells up to 1000 nM. CKI-8 did not affect alkaline phosphatase activity as well the mineralization induced by Saos-2 cells and by primary osteoblasts. CKI-13 decreased by 35% the mineralization induced by Saos-2 cells while it did not on mineralization induced by primary osteoblasts. Addition of CKI-13 decreased alkaline phosphatase activity by around 20% (Saos-2 cells) and 45% (primary osteoblasts). Bone resorption on bovine slices decreased significantly with 10 nM of CKI-13, with 100 nM of CKI-8 and commercial inhibitor E64. Our findings indicated that CKI-8 and CKI-13 inhibited bone resorption and affected the mobility of osteoclast. To monitor directly the PPi hydrolytic activity by alkaline phosphatase, we developed an infrared (IR) assay taking the advantage to use natural substrate under physiological pH in matrix vesicles and in living cells. PPi band located at 1107 cm-1 (∑= 2158 ± 211 M-1.cm-1) and Pi bands located at 1076 cm-1 (∑= 1346 ± 116 M-1.cm-1) and at 991 cm-1 (∑= 493 ± 49 M-1.cm-1) served to measure the substrate and the product concentrations
Subedi, Yagya P. "Cost-Effective Synthesis, Bioactivity and Cellular Uptake Study of Aminoglycosides with Antimicrobial and Connexin Hemichannel Inhibitory Activity." DigitalCommons@USU, 2019. https://digitalcommons.usu.edu/etd/7699.
Повний текст джерелаLau, Rosanna. "cIAP2 Negatively Regulates Proliferation and Tumourigenesis by Repressing IKK Activity and Maintaining p53 Function." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/22845.
Повний текст джерелаPosarac, Vesna. "Characterization and anti-HIV activity of the proprotein convertase-directed serine protease inhibitor, Spn4A." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/3434.
Повний текст джерелаOrdway, Gregory A., W. D. Gill, J. B. Coleman, Hui Wang-Heaton, and Russell W. Brown. "Anti-Inflammatory PARP Inhibitor Demonstrates Antidepressant Activity in Animal Model of Treatment Resistant Depression." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/8643.
Повний текст джерелаCouto, Jason. "Biologic Activity of the Novel Small Molecule STAT3 Inhibitor Against Canine Osteosarcoma Cell Lines." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1373986927.
Повний текст джерелаHewitt, Laura. "Using a novel small molecule inhibitor to investigate the role of Mps1 kinase activity." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/using-a-novel-small-molecule-inhibitor-to-investigate-the-role-of-mps1-kinase-activity(fcacfefc-90d9-4e92-9af4-a57897737329).html.
Повний текст джерелаWatanabe, Koji. "Pterin-6-aldehyde, an Inhibitor of Xanthine Oxidase, Has Superoxide Anion Radical Scavenging Activity." Kyoto University, 2000. http://hdl.handle.net/2433/151411.
Повний текст джерелаBosc, Damien. "Synthèse et évaluation biologique d’hétérocycles à cinq chaînons, inhibiteurs de la protéine farnésyltransférase." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112200/document.
Повний текст джерелаProtein farnesyltransferase (FTase) is a zinc metalloenzyme which catalyzes the transfer of a farnesyl chain from farnesyl pyrophosphate (FPP) to the cysteine residue of some proteins possessing a C-terminal CaaX moiety where C is the farnesylated cysteine, a is an aliphatic amino-acid and X is Ser, Ala, Gln or Met. Once attached, the farnesyl group serves as anchors for fixing proteins to cell membrane and as molecular handles for facilitating binding of these prenylated proteins to other proteins.First studied in oncology, FTase constitutes nowadays a potential target for antiparasitic therapies, where drugs are missing due to the appearance of resistance phenomena. The necessity to improve the existing therapies paves the way of innovating researches to find new bioactive molecules.During this Ph.D work, two strategies of research used in medicinal chemistry were performed.The first approach consisted in the synthesis of bisubstrate analogues with a 1,2,3-triazole core deviced to tie up both to the protein and the FPP binding sites. This rational approach also allowed to draft a one-pot synthesis of 1,5-disubstituted triazoles from primary amines.The screening approach was the second strategy to search for new inhibitors. For this purpose, ICSN chemical library was screened and two 3-arylthiophene compounds disclosed good activities and an original scaffold for FTase inhibition. Therefore, a structure-activity relationship study was carried out to modulate the different positions of the thiophene and the nature of the central heterocycle.This work allowed us to create a above-hundred-molecule library. The biological evaluation of these analogues on human and T. brucei isolated FTase and on T. brucei and P. falciparum parasites revealed particularly interesting and promising molecules
Li, Hao. "Design, Synthesis, and Structure-Activity Relationship Investigation of Selective Sphingosine Kinase Inhibitors." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/100741.
Повний текст джерелаDoctor of Philosophy
Baker, Amanda F., Neale T. Hanke, Barbara J. Sands, Liliana Carbajal, Janet L. Anderl, and Linda L. Garland. "Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell and small cell lung cancer models." BioMed Central, 2014. http://hdl.handle.net/10150/610318.
Повний текст джерелаChandrasekar, Balakumaran [Verfasser]. "From glycosidase activity profiling to inhibitor discovery in the plant pathogen Pseudomonas syringae / Balakumaran Chandrasekar." Bonn : Universitäts- und Landesbibliothek Bonn, 2018. http://d-nb.info/1161462309/34.
Повний текст джерелаYunus, Madiha. "Investigating the Effect of Regorafenib on the Expression and Activity of the Angiogenesis-Modulating Receptor Tyrosine Kinases." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29860.
Повний текст джерелаWang, Haiyao. "Antiplasmin the main plasmin inhibitor in blood plasma : studies on structure-function relationships /." Stockholm : Department of Surgical Sciences, Division of Clincal Chemistry and Blood Coagulation, Karolinska University, 2005. http://diss.kib.ki.se/2005/91-7140-278-0/.
Повний текст джерелаFernández, Cecilia A. 1969. "Functional and structural uncoupling of the angiogenic and enzymatic inhibitory activity of TIMPs : loop 6 of TIMP-2 is a novel inhibitor of angiogenesis." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/31110.
Повний текст джерелаIncludes bibliographical references (leaves 119-130).
Tissue inhibitors of metalloproteinases (TIMPs) regulate tumor growth, progression and angiogenesis in a variety of experimental cancer models and in human malignancies. However, numerous studies have revealed important differences between TIMP family members in their ability to inhibit angiogenic processes in vitro and angiogenesis in vivo despite their universal ability to inhibit matrix metalloproteinase (MMP) activity. To address these differences, structure-function studies were conducted to identify and characterize the anti-angiogenic domains of TIMP-2, the endogenous MMP inhibitor that uniquely inhibits capillary endothelial cell (EC) proliferation and angiogenesis in vivo. Only the carboxy-terminal domain of TIMP-2 (T2C) and not the MMP-inhibitory N-terminal domain (T2N), inhibited capillary EC proliferation. Although both T2N and T2C inhibited embryonic angiogenesis, only T2C potently inhibited mitogen-stimulated angiogenesis. These findings demonstrate that TIMP-2 possesses two distinct types of anti-angiogenic activities which can be uncoupled from each other. The anti-proliferative activity of T2C was further mapped to the 24-amino acid peptide, Loop 6, which proved to be a potent inhibitor of both embryonic and nitogen-stimulated angiogenesis in vivo. Initial studies into the mechanism(s) by which Loop 6 inhibits angiogenesis revealed that the anti-proliferative effects of Loop 6 are due, at least in part, to the inhibition of cell cycle progression and not to the induction of apoptosis. This inhibition was associated with increased levels of cell cycle inhibitor p27. Although Loop 6 did not compete with bFGF for binding to its receptor,
(cont.) five potential cell surface complexes were observed in crosslinking studies of capillary EC treated with ¹²⁵I-labeled T2C or Loop 6. Finally, given the high degree of homology between TIMP-2 and TIMP-4, we hypothesized that TIMP-4 might share anti-proliferative and MMP inhibition- independent anti-angiogenic activities with TIMP-2. Our results demonstrate that although TIMP-4 inhibits capillary EC migration, it does not inhibit capillary EC proliferation. Furthermore, TIMP-4 did not result in significant inhibition of embryonic angiogenesis in the CAM. These results suggest that TIMP-2 is unique among TIMP family members in its ability to inhibit angiogenesis via two distinct pathways. One of these activities, housed within Loop 6, results in the potent inhibition of angiogenesis in vivo.
by Cecilia A. Fernández.
Ph.D.in Applied Biosciences
Natarajan, M. "Effects of amylase inhibitor albumin from wheat on the alpha-amylase activity in carp and tilapia." Thesis, University of Stirling, 1988. http://hdl.handle.net/1893/1919.
Повний текст джерелаGlas, Carina [Verfasser], and Franz [Akademischer Betreuer] Bracher. "Structure-activity relationship analysis of the subtype-selective Sirt5 inhibitor balsalazide / Carina Glas ; Betreuer: Franz Bracher." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1228270929/34.
Повний текст джерелаTanaka, Ruriko. "Activity of the multi-targeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL positive leukemic cells." Kyoto University, 2011. http://hdl.handle.net/2433/142109.
Повний текст джерелаBatman, Angela. "MODULATION OF COCAINE-LIKE BEHAVIOURAL ACTIVITY BY SEROTONIN UPTAKE INHIBITION RELATIVE TO THE EFFECTS OF THE NOVEL AND SELECTIVE DOPAMINE TRANSPORTER INHIBITOR, D-84." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2181.
Повний текст джерелаDebord, Jean. "Relation structure chimique-activité biologique pour quelques phosphoramides et benzamides." Poitiers, 1988. http://www.theses.fr/1988POIT2331.
Повний текст джерелаRen, Huan. "Biological activity of the 2-phenylaminopyrimidine class receptor tyrosine kinase inhibitor imatinib mesylate (STI571) in malignant glioma." Thesis, University of Liverpool, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419008.
Повний текст джерелаZyryanova, Alisa. "A molecule-inhibitor of the integrated stress response regulates activity of mammalian eukaryotic translation initiation factor 2B." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/284208.
Повний текст джерелаHarrington, Bonnie K. "Activity of the Second Generation BTK Inhibitor Acalabrutinib in Canine and Human B-cell Non-Hodgkin Lymphoma." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1531911818180297.
Повний текст джерелаGarrido, Christian M. "Avicin is a potent sphingomyelinase inhibitor that blocks K-Ras plasma membrane interaction and its oncogenic activity." Wright State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1545974237243977.
Повний текст джерелаKhanwalkar, Harshal. "In vitro and in vivo analysis of anti-tumour activity of UVI5008, a novel chromatin enzyme inhibitor." Strasbourg, 2010. http://www.theses.fr/2010STRA6266.
Повний текст джерелаIt is becoming increasingly clear that cancer is a consequence not only of genetic but also of epigenetic alterations. Interestingly, this epigenetic deregulation is reversible making the corresponding enzymes promising drug targets. Chromatin modifying enzymes, in particular histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), have recently emerged as new promising targets of the so-called “epigenetic drugs” for the treatment of cancer. The aim of this project is to characterize the activities of UVI 5008, a derivative of psammaplin A, a natural product that was originally isolated from the marine sponge Psammaplysilla sp. This compound was synthesized by one of our collaborators, Prof. Angel. R de Lera’s lab (Vigo University, Spain) and we were able to show that it targets several epigenetic effector enzymes and displays anti-tumour activity in vitro and in vivo. We have assessed the tumoricidal activity of UVI5008 both in vitro in a panel of cancer cell lines as well as ex vivo in leukemia patient’s blasts. Our results indicate that UVI5008 reduces cell proliferation by inducing G1-M arrest and apoptosis in established acute myeloid leukemia (AML) cells and AML patient’s blasts in ex vivo culture. In vitro enzymatic assays showed that UVI5008 blocks HDAC1, 4 and 6 as well as increases the global and site-specific histone acetylation. Apart from its HDAC inhibitory activity, the novel inhibitor blocks CpG island methylation of the promoters of p16/INK4 and retinoic acid receptors (RAR)-beta tumor suppressors. Moreover, we have observed that UVI5008 has sirtuin inhibitory capacity as it increases the acetylation levels of p53 on lysine 382 residue. We could also show that UVI5008 exerts its antitumor effect in vivo in HCT-116 (human colon cancer) and MCF-7 (human breast cancer) xenografted tumours in nude mice as well as in a mouse breast cancer model MMTV-myc, which was accompanied by increased histone and p53K382 acetylation in tumouri. Importantly, UVI5008 anti-tumoral activity is selective for cancer cells, without significant toxicity to normal cells and is p53-independent which is also promising, as in the majority of cancers p53 is either silenced or mutated. It is well documented that ErbB2 gene plays an important role in human malignancies. It is amplified and /or overexpressed in approximately 30% of human breast carcinomas and in many other types of human malignancies and individuals with ErbB2-overexpressing tumours have significantly poor clinical outcome. Taking into consideration this fact, we have assessed the anti tumour activity of UVI5008 in one more mouse breast cancer model MMTV-ErbB2, which revealed that UVI5008 is equally active in ErbB2 overexpressing breast tumours. To date there is not a single drug that simultaneously targets all these three families of enzymes namely HDACs, DNMTs and SIRTs. Taken together, our data strongly suggest that targeting these enzymes simultaneously by a single drug is a feasible and an attractive paradigm for new cancer therapies
ARNO', BARBARA. "Investigation of human topoisomerase 1b activity through a domain substitution and interaction with a new synthetic inhibitor." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2013. http://hdl.handle.net/2108/210054.
Повний текст джерелаPlasmodium falciparum infection is one of the most frequent acquired red blood cell disease worldwide. The spread of multi-drug-resistant strains has increased the need to identify new molecular targets for antimalarial therapy. DNA topoisomerases may be considered possible candidates, due to their important role in cellular activities, including DNA replication. DNA topoisomerase I (Top1) relaxes supercoiled DNA by a transient DNA strand breakage, rotation, and religation. The human Top1 (hTop1) comprises a conserved protein clamp, tightly wrapped about the DNA duplex, formed by three protein domains and an extended coiled-coil linker domain that appropriately positions the C-terminal active site tyrosine against the core to form the catalytic pocket. The linker has been shown to be important in controlling the enzyme catalytic mechanism. After removal of the linker domain, hTop1 loses inter-domain communication, thus highlighting the importance of linker in controlling the religation and modulating CPT sensitivity. The Plasmodium falciparum topoisomerase I (PfTop1) contains a longer linker, compared to the human homologue. This finding pushed us in exploiting its structural and functional properties in enzyme activity and drug sensitivity swapping the hTop1 linker domain with the corresponding one of PfTop1. Moreover, as the linker domain specifically affects the religation reaction, a pentaciclic-diquinoid synthetic compound, KuQ, has been designed and its effect has been analyzed through activity assays and molecular docking, identifying crucial elements for this step of the hTop1 activity.
Boisson, Julien. "Synthèse de nouveaux iminosucres et évaluation de leur activité inhibitrice de glycosidases." Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENV027/document.
Повний текст джерелаThis manuscript describes the synthesis and bioevaluation of 10 new iminosugars. Iminosugars are an important class of compounds, which can inhibit the activity of glycosidases (enzymes which catalyze oligosaccharide hydrolysis). The inhibitory activity of our products was assessed towards a panel of 7 glycosidases.Our laboratory has recently succeeded in the preparation of polyalkoxylated cyclic ketonitrones from ketoses such as D-fructose or L-sorbose (abundant natural sugars). Herein, we envisaged their utilization as precursors of new, structurally original iminosugars, bearing a quaternary center in of their nitrogen atom. We firstly improved the synthesis of these ketonitrones, and then we optimized conditions for their diastereoselective C-vinylation, in order to access selectively and efficiently four diastereoisomeric piperidines after reduction of the formed N-hydroxylamine function. The N-allylation of these piperidines gave access to the corresponding bis-alkenylpiperidines, which were readily transformed into ,alpha-gem-disubstituted tetrahydroxylated N-propylpiperidines after hydrogenation (of both unsaturated chains) and debenzylation.The bis-alkenylpiperidines were also engaged in a ring closing metathesis reaction, providing the indolizidine skeleton with a double bond in C1-C2. Hydrogenation or dihydroxylation of the latter, followed by a debenzylation step, produced original polyhydroxylated indolizidines (tetra- and hexahydroxylated), which are substituted at their ring junction (8a position). One of the synthesized compounds (an indolizidine) was found to be a highly potent and selective inhibitor of -glucosidases with a median inhibitory concentration of 52 nM (rice alpha-glucosidase) and an uncommon mode of inhibition for this class of molecules (mixed non-competitive inhibition)
Kutlesa, Nicole J. "The insecticidal activity of a herbicidal inhibitor of glutamine synthetase tested on larvae of Calpodes ethlius (Lepidoptera: hersperiidae)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ42166.pdf.
Повний текст джерелаHenderson, Sally E. "Translating the Anti-Tumor/Anti-Cachectic Activity of AR-42, a Novel HDAC Inhibitor, into Pancreatic Cancer Therapy." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1495801301660324.
Повний текст джерелаChristadore, Lisa M. "Discovery of a small molecule dihydroquinolinone inhibitor with potent antiproliferative and antitumor activity results in catastrophic cell division." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12733.
Повний текст джерелаA family of dihydroquinolinones that inhibited the proliferation of a number of cancer cell lines and targeted the oncogenic activities of the late simian virus 40 factor (LSF) was discovered. The lead quinolinone inhibitors, 8-(2-propoxyphenyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]quinolin-6(5H)-one, FQI1, and 8-(2-propoxyphenyl)-[1,3]dioxolo[4,5-g]quinolin-6(5H)-one, FQI2, were determined by a comprehensive SAR study. The lead compounds had low micromolar to nanomolar Gi50S and IC50S (concentrations that induced 50% inhibition) in cell growth and LSF-directed luciferase reporter assays, respectively. A distinct correlation between the GI50 and IC50 values indicated antiproliferative effects resulted from inhibition of LSF activity. FQI1 had no growth effects on immortalized human hepatocytes or primary mouse hepatocytes. Overall, FQI1 proved a good drug candidate for hepatocellular carcinoma (HCC). It possessed a low molecular weight and moderate solubility, which was improved by substitution of the amide with a triazole bioisostere. FQI1 showed excellent microsomal stability, high in vivo volume of distribution and half-life in rodents, and was a potent inhibitor of HCC tumorigenesis in immunocompromised mice. FQI1 induced mitotic catastrophe in the HCC cell line, QGY-7703, the cervical carcinoma cell line, HeLa, and the NIH-3T3 fibroblasts, as evidenced by widespread multinucleated cell morphologies. Excessive micronucleation in NIH-3T3 cells treated with higher FQI1 concentrations further supported severe chromosome segregation defects. Mitotic slippage into interphase and subsequent endoreduplication was also induced by FQI1 in NIH-3T3 cells. These phenotypes have been seen with chemicals such as the microtubulin poisons and Aurora B kinase inhibitors. Together these results suggested that FQI1-induced evasion or adaptation of the spindle assembly checkpoint and abnormal chromosome segregation resulted in mitotic catastrophe, and in the case of NIH-3T3 cells, polyploid cell progeny. Expression profiling in QGY-7703 cells with FQI1 cells revealed an upregulation of multiple genes along the TGF-β/SMAD signaling cascade compared to the untreated cell population. This supported a model where the induction of p21Cip1 activity as a result of mitotic slippage activated the G1/S checkpoint in response to aberrant exit out of mitosis in QGY-7703 cells. These results together elucidated FQI1's mechanism of action in mitosis and also strongly suggested that LSF regulated genes required for the proper execution of mitosis.
Elkovich, Andrea J. "The DNA methyltransferase inhibitor, guadecitabine, targets tumor-induced myelopoiesis and recovers T cell activity to slow tumor growth." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5792.
Повний текст джерелаCrosby, Brendan. "Exercise as an adjunct therapy in melanoma patients undergoing checkpoint inhibitor therapy." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2022. https://ro.ecu.edu.au/theses/2569.
Повний текст джерелаSouza, Pedro Filho Noronha de. "Purification, biochemical characterization and antimicrobial activity of a novel 2s albumin from castor bean(ricinus cmmunis L.) cake displaying trypsin inhibitory activity." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8867.
Повний текст джерелаConselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico
Castor bean (Ricinus communis L.) is an important crop for the Northeast of Brazil, which recently has been used to produce biodiesel. Around 90% of the castor bean production in Brazil is concentrated at Northeast region and the state of Cearà is the second largest producer. During the oil extraction process from the castor bean seeds, a resulting residue, called castor cake, is underutilized. However, this byproduct is rich in protein and micronutrients such as nitrogen, phosphorus and potassium, an attribute that qualifies it as a stuff that could be used as organic fertilizer or as animal feed, for example, bringing added value to it. Unfortunately, its use as food has not been possible because of the presence of toxic elements and allergens (ricin, ricinine, complex allergens) in its composition, unless it were previously submitted to a detoxification process. To date, the existing technologies to this end are not economically viable on an industrial scale. Therefore, studies to add value to this abundant byproduct generated in the castor bean biodiesel productive chain is of paramount importance. Thus, in this context, this study was performed to identify, isolate, purify and characterize new bioactive molecules of de-oiled castor cake with biotechnological potential. Through extraction of soluble proteins with 50 mM Tris-HCl pH 7.5, fractionation with ammonium sulfate (50-75%), following by hydrophobic interaction chromatography in Phenyl-Sepharose column and ion exchange chromatography (DEAE-Sepharose), a protein, named Rc-2S-Alb, able to inhibit trypsin was purified. Rc-2S-Alb has a molecular mass of approximately 75.8 kDa, as determined by SDS-PAGE, and under reducing conditions showed a large and a small protein band of 15.8 kDa and 10.5 kDa, respectively. Its NH2-terminal sequence showed similarity with the following proteins: putative 2S albumin precursor (89%), chain A of RicC3 (89%), and chain A of mabilin-1 (89%), all from R. communis seeds; and with the short chain of a "napin-like" protein from Brassica napus (89%). In addition, these similar proteins have two highly conserved domains: QEVQRKDLS and YLRQS. Comparison of the partial primary structure of Rc-2S-Alb generated by the ESI-Q-TOF MS/MS analysis of 17 tryptic peptides, showed 43% similarity to Mabinlin-1 (pI/Mr 6.7 and 29.3 kDa) from R. communis. There were also high similarities among the three-dimensional structures of Rc-2S-Alb, RicC3 and Mabinlin-1. Rc-2S-Alb did not inhibit the spore germination of the phytopathogenic fungi Fusarium oxysporum and Rizoctonia solani, but promoted aggregation of their respective spores. Moreover, Rc-2S-Alb did not inhibit the mycelial growth of Fusarium oxysporum, Fusarium solani, Rizoctonia solani and Collethotricum gloeosporioides. Contrary, Rc-2S-Alb was effective in inhibiting the growth of the human pathogenic bacteria Pseudomonas aeruginosae, Klebsiella pneumoniae and Bacillus subtilis, at low concentrations. In conclusion, it was established a protocol to purify a new 2S albumin from castor bean cake, which inhibits trypsin and has important antibacterial activity. Thus, the Rc-2S-Alb should be further studied in order to verify its effectiveness as new alternative therapeutic agent against resistant bacteria to commercial antibiotics, which will contribute to improve the human health.
A mamoneira (Ricinus communis L.) à uma cultura importante para a regiÃo Nordeste do Brasil, onde, recentemente, tem sido utilizada para produÃÃo de biodiesel. O Nordeste detÃm 90% da produÃÃo brasileira de mamona, sendo o CearÃ, o segundo maior produtor. No processo de extraÃÃo de Ãleo das sementes de mamoneira para produÃÃo de biodiesel, o resÃduo resultante, denominado de torta da mamona, representa um subproduto pouco utilizado. Apesar disso, essa torta à rica em proteÃnas e micronutrientes, como nitrogÃnio, fÃsforo e potÃssio, atributo que a qualifica como um insumo que poderia ser utilizado como adubo orgÃnico, ou mesmo como raÃÃo animal, o que lhe agregaria valor comercial. Todavia, seu uso como alimento nÃo tem sido possÃvel por causa da presenÃa de elementos tÃxicos e alergÃnicos (Ricina, Ricinina, Complexos AlergÃnicos) na sua composiÃÃo, a nÃo ser que passasse por processamento para sua destoxificaÃÃo. Infelizmente, tecnologia economicamente viÃvel para esse fim, em escala industrial, ainda à inexistente. Portanto, hà necessidade de pesquisas que venham a agregar valor a esse subproduto abundante da cadeia produtiva do biodiesel. Assim, nesse contexto, o presente trabalho està inserido num projeto cujo objetivo maior à identificar, isolar, purificar e caracterizar novas molÃculas bioativas da torta delipidada de sementes de mamoeira com potencial biotecnolÃgico. AtravÃs de extraÃÃo de proteÃnas solÃveis com tampÃo Tris-HCl, 50 mM, pH 7,5, e fracionamento do extrato obtido com sulfato de amÃnio (50-75%), cromatografia de interaÃÃo hidrofÃbica em coluna Phenyl-Sepharose e cromatografia de troca iÃnica (DEAE-Sepharose) foi possÃvel purificar uma albumina 2S, denominada Rc-2S-Alb, capaz de inibir tripsina. A Rc-2S-Alb apresentou massa molecular de, aproximadamente, 75,8 kDa, determinada por SDS-PAGE, mas, em condiÃÃes redutoras, apareceu como uma banda maior de 15,8 kDa e outra menor com 10,5 kDa. Sua sequÃncia NH2-terminal revelou haver similaridade (89%) com o precursor putativo da albumina 2S de R. communis jà descrita, com a cadeia A da estrutura da RicC3 (89%), com a cadeia A da mabilin-1, ambas, tambÃm, de R. communis (89%), com a cadeia pequena de uma proteina ânapin-likeâde Brassica napus (89%). Em todas essas proteÃnas similares, dois domÃnios, QEVQRKDLS e YLRQS, sÃo altamente conservados. ComparaÃÃo da estrutura primÃria gerada por ESI-Q-TOF MS/MS, a apartir de 17 peptÃdeos trÃpticos da Rc-2S-Alb, mostrou similaridade de 43% com a Mabinlin-1 (pI/Mr de 6,7 e 29.3 kDa) de R. communis. Em relaÃÃo à estrutura tridimensional da Rc-2S-Alb, ela apresentou similaridade com a de Ric C3 e Mabinlin-1. A Rc-2S-Alb foi incapaz de inibir a germinaÃÃo de esporos dos fungos fitopatogÃnicos Fusarium oxysporum e Rizoctonia solani, mas foi capaz de promover a aglomeraÃÃo dos mesmos. A Rc-2S-Alb tambÃm nÃo foi capaz de inibir o crescimento micelial dos fungos Fusarium oxysporum, Fusarium solani, Rizoctonia solani e Collethotricum gloeosporioides. Por outro lado, a Rc-2S-Alb foi eficiente em inibir o crescimento de Pseudomonas aeruginosae, Klebsiella pneumoniae e Bacillus subtilis, todas as bactÃrias patogÃnicas a seres humanos, quando em baixas concentraÃÃes. Como conclusÃo, foi possÃvel a purificaÃÃo de uma nova albumina 2S da torta da mamona, capaz de inibir tripsina e com atividade antibacteriana importante. Assim, a Rc-2S-Alb deve ser explorada no sentido de verificar sua eficÃcia como um novo agente terapÃutico alternativo no combate a bactÃrias resistentes aos produtos disponÃveis, hoje, no mercado, o que, se confirmado, poderà contribuir para a melhoria da saÃde humana.
Byberg, Liisa. "Plasminogen Activator Inhibitor-1 and the Insulin Resistance Syndrome." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5307-4/.
Повний текст джерелаBöhm, Miriam [Verfasser]. "Targeting the Final Step of Blood Coagulation : Structure-Activity-Relationship Studies on the Factor XIIIa Inhibitor Tridegin / Miriam Böhm." Bonn : Universitäts- und Landesbibliothek Bonn, 2015. http://d-nb.info/1077290438/34.
Повний текст джерелаShimura, Kazuya. "Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137)." Kyoto University, 2008. http://hdl.handle.net/2433/135828.
Повний текст джерелаBlanco, Aparicio Carmen. "El Inhibidor de carboxipeptidasa de patata (PCI): un antagonista del EGF con actividad antitumoral." Doctoral thesis, Universitat de Girona, 1998. http://hdl.handle.net/10803/96759.
Повний текст джерелаEn el presente trabajo se ha demostrado que el inhibidor de carboxipeptidasa de patata (PCI) tiene un efecto inhibitorio sobre el crecimiento tumoral tanto in vitro como in vivo, y se ha estudiado su mecanismo de acción, lo que ha llevado a descubrir que el PCI es un antagonista del EGF. Con dicho fin se han utilizado técnicas de cultivo celular en conjunción con técnicas bioquímicas, de biología molecular, de análisis computacional y ensayos con modelos animales
En el present treball s’ha demostrat que l’inhibidor de carboxipeptidasa de patata (PCI) té un efecte inhibitori sobre el creixement tumoral tant in vitro com in vivo i s’ha estudiat el seu mecanisme d’acció, que ha permès descobrir que el PCI és un antagonista de l’EGF. Amb aquest fi s’han utilitzat tècniques de cultiu cel·lular amb tècniques bioquímiques, de biologia molecular, d’anàlisi computacional i assajos amb models animals
GALBIATI, ANDREA. "DESIGN AND SYNTHESIS OF NOVEL ENZYME INHIBITORS AS ANTIPROLIFERATIVE COMPOUNDS WITH ANTIPROTOZOAL AND ANTICANCER ACTIVITY." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/827428.
Повний текст джерелаDias, Lucas Pinheiro. "PurificaÃÃo e caracterizaÃÃo de um inibidor de tripsina das flores de Cassia fistula Linn. com atividade antimicrobiana." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16457.
Повний текст джерелаAs plantas sintetizam proteÃnas que possuem propriedades antimicrobianas, podendo ser utilizadas em substituiÃÃo aos defensivos quÃmicos no campo e como fonte de novas drogas para o controle de infecÃÃes bacterianas em humanos. Dentre as diversas estruturas vegetais, ÃrgÃos reprodutivos como as flores parecem ser uma fonte promissora de tais molÃculas ativas contra patÃgenos, particularmente se considerado o seu relevante papel fisiolÃgico, o qual deve ser preservado. Nesse contexto, a presente pesquisa experimental teve como objetivos a prospecÃÃo de proteÃnas com aÃÃo antimicrobiana em flores silvestres e posterior purificaÃÃo, caracterizaÃÃo bioquÃmica e avaliaÃÃo da atividade antimicrobiana de um inibidor de tripsina presente em flores de Cassia fistula Linn. (Chuva-de-ouro). O extrato total das flores de C. fistula foi preparado em tampÃo fosfato de sÃdio 50 mM, pH 7,5. Esse extrato apresentou atividade inibitÃria de tripsina (42,41 Â 0,35 UI/mgP) e de papaÃna (27,10 Â 0,23 UI/mgP), alÃm de mostrar a presenÃa de peroxidase (20,0 Â 0,18 UAP/mgP) e quitinase (1,70 Â 0,21 ηkatal/mgP), estando ausentes as atividades hemaglutinante, β-1,3-glucanÃsica, ureÃsica e proteÃsica. O inibidor de tripsina de C. fistula, denominado CfTI, foi purificado do extrato total por fracionamento com Ãcido tricloroacÃtico (2,5%), seguido de cromatografias de afinidade (anidrotripsina-Sepharose-4B) e fase reversa (Vydac C-18TP 522). CfTI Ã uma glicoproteÃna com massa molecular aparente de 22,2 kDa, pI 5,0 e sequÃncia NH2-terminal exibindo alta similaridade com o inibidor de tripsina da soja do tipo Kunitz (SBTI). O inibidor mostrou-se pouco estÃvel ao calor, reduzindo sua atividade inibitÃria para 23,4% quando incubado a 60 ÂC, durante 15 minutos. No entanto, ele se mostrou bastante estÃvel a variaÃÃes no pH. CfTI (100 Âg/mL) retardou o crescimento dos fungos fitopatogÃnicos de importÃncia agrÃcola, Colletotrichum lindemuthianum e Fusarium solani, alÃm de apresentar atividade antibacteriana frente Ãs bactÃrias patogÃnicas ao homem, Staphylococcus aureus e Enterobacter aerogenes. Os resultados obtidos demonstram o potencial das flores como fonte diversificada de proteÃnas bioativas, evidenciando o inibidor de tripsina presente em flores de C. fistula, fomentando sua aplicaÃÃo biotecnolÃgica frente a fungos e bactÃrias de relevÃncia para a Agricultura e SaÃde.
Plants synthesize proteins that have antimicrobial properties, which can be used to substitute chemical pesticides in agriculture and as new drugs for the control of bacterial infections in humans. Among the various plant structures, the flowers seem to be a promising source of active molecules against pathogens, particularly if considered its important physiological role, which should be preserved. Therefore, this experimental research aimed at the prospection of novel proteins with antimicrobial activity in wild flowers and to subsequent purification, biochemical characterization and evaluation of antimicrobial activity of a trypsin inhibitor present in flowers of Cassia fistula Linn (the golden shower tree). The total extract of C. fistula flowers was prepared in 50 mM sodium phosphate buffer, pH 7.5. This extract presented trypsin inhibitory activity (42.41 Â 0.35 IU/mgP) and papain (27.10 Â 0.23 IU/mgP), besides to the presence of peroxidase (20.0 Â 0.18 UAP/mgP) and chitinase (1.70 Â 0.21 ηkatal/mgP). On the other hand, the hemagglutinating, β-1,3-glucanase, protease and urease activities were not detected. The trypsin inhibitor of C. fistula, named CfTI, was purified by fractionating the crude extract with trichloroacetic acid (2.5%) followed by affinity (anidrotripsina-Sepharose-4B) and reverse phase (Vydac C-18TP 522) chromatographies. CfTI is a glycoprotein with an apparent molecular mass of 22.2 kDa, pI 5.0 and NH2-terminal sequence showing high similarity with Kunitz soybean trypsin inhibitor (SBTI). The inhibitor was not stable to heat, and loss 23.4% when incubated at 60 ÂC for 15 minutes. However, it proved to be stable to changes of pH. CfTI (100 Âg/mL) slowed the growth of pathogenic fungi of agricultural importance, Colletotrichum lindemuthianum and Fusarium solani, and also presented antibacterial activity against the human pathogenic bacteria, Staphylococcus aureus and Enterobacter aerogenes. The results demonstrate the potential of the flowers as a source of diverse bioactive proteins, as the trypsin inhibitor present in C. fistula flowers, promoting its biotechnological potential application against fungi and bacteria of relevance to Agriculture and human health.
Dias, Lucas Pinheiro. "Purificação e caracterização de um inibidor de tripsina das flores de Cassia fistula Linn. com atividade antimicrobiana." reponame:Repositório Institucional da UFC, 2012. http://www.repositorio.ufc.br/handle/riufc/18870.
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Plants synthesize proteins that have antimicrobial properties, which can be used to substitute chemical pesticides in agriculture and as new drugs for the control of bacterial infections in humans. Among the various plant structures, the flowers seem to be a promising source of active molecules against pathogens, particularly if considered its important physiological role, which should be preserved. Therefore, this experimental research aimed at the prospection of novel proteins with antimicrobial activity in wild flowers and to subsequent purification, biochemical characterization and evaluation of antimicrobial activity of a trypsin inhibitor present in flowers of Cassia fistula Linn (the golden shower tree). The total extract of C. fistula flowers was prepared in 50 mM sodium phosphate buffer, pH 7.5. This extract presented trypsin inhibitory activity (42.41 ± 0.35 IU/mgP) and papain (27.10 ± 0.23 IU/mgP), besides to the presence of peroxidase (20.0 ± 0.18 UAP/mgP) and chitinase (1.70 ± 0.21 ηkatal/mgP). On the other hand, the hemagglutinating, β-1,3-glucanase, protease and urease activities were not detected. The trypsin inhibitor of C. fistula, named CfTI, was purified by fractionating the crude extract with trichloroacetic acid (2.5%) followed by affinity (anidrotripsina-Sepharose-4B) and reverse phase (Vydac C-18TP 522) chromatographies. CfTI is a glycoprotein with an apparent molecular mass of 22.2 kDa, pI 5.0 and NH2-terminal sequence showing high similarity with Kunitz soybean trypsin inhibitor (SBTI). The inhibitor was not stable to heat, and loss 23.4% when incubated at 60 °C for 15 minutes. However, it proved to be stable to changes of pH. CfTI (100 µg/mL) slowed the growth of pathogenic fungi of agricultural importance, Colletotrichum lindemuthianum and Fusarium solani, and also presented antibacterial activity against the human pathogenic bacteria, Staphylococcus aureus and Enterobacter aerogenes. The results demonstrate the potential of the flowers as a source of diverse bioactive proteins, as the trypsin inhibitor present in C. fistula flowers, promoting its biotechnological potential application against fungi and bacteria of relevance to Agriculture and human health.
As plantas sintetizam proteínas que possuem propriedades antimicrobianas, podendo ser utilizadas em substituição aos defensivos químicos no campo e como fonte de novas drogas para o controle de infecções bacterianas em humanos. Dentre as diversas estruturas vegetais, órgãos reprodutivos como as flores parecem ser uma fonte promissora de tais moléculas ativas contra patógenos, particularmente se considerado o seu relevante papel fisiológico, o qual deve ser preservado. Nesse contexto, a presente pesquisa experimental teve como objetivos a prospecção de proteínas com ação antimicrobiana em flores silvestres e posterior purificação, caracterização bioquímica e avaliação da atividade antimicrobiana de um inibidor de tripsina presente em flores de Cassia fistula Linn. (Chuva-de-ouro). O extrato total das flores de C. fistula foi preparado em tampão fosfato de sódio 50 mM, pH 7,5. Esse extrato apresentou atividade inibitória de tripsina (42,41 ± 0,35 UI/mgP) e de papaína (27,10 ± 0,23 UI/mgP), além de mostrar a presença de peroxidase (20,0 ± 0,18 UAP/mgP) e quitinase (1,70 ± 0,21 ηkatal/mgP), estando ausentes as atividades hemaglutinante, β-1,3-glucanásica, ureásica e proteásica. O inibidor de tripsina de C. fistula, denominado CfTI, foi purificado do extrato total por fracionamento com ácido tricloroacético (2,5%), seguido de cromatografias de afinidade (anidrotripsina-Sepharose-4B) e fase reversa (Vydac C-18TP 522). CfTI é uma glicoproteína com massa molecular aparente de 22,2 kDa, pI 5,0 e sequência NH2-terminal exibindo alta similaridade com o inibidor de tripsina da soja do tipo Kunitz (SBTI). O inibidor mostrou-se pouco estável ao calor, reduzindo sua atividade inibitória para 23,4% quando incubado a 60 °C, durante 15 minutos. No entanto, ele se mostrou bastante estável a variações no pH. CfTI (100 µg/mL) retardou o crescimento dos fungos fitopatogênicos de importância agrícola, Colletotrichum lindemuthianum e Fusarium solani, além de apresentar atividade antibacteriana frente às bactérias patogênicas ao homem, Staphylococcus aureus e Enterobacter aerogenes. Os resultados obtidos demonstram o potencial das flores como fonte diversificada de proteínas bioativas, evidenciando o inibidor de tripsina presente em flores de C. fistula, fomentando sua aplicação biotecnológica frente a fungos e bactérias de relevância para a Agricultura e Saúde.
Recasens, Zorzo Clara. "Preclinical evaluation of the antitumor activity of a new CXCR4 inhibitor: a novel therapeutic approach in diffuse large B-cell lymphoma." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663897.
Повний текст джерелаLa activación constitutiva del receptor de quemocinas CXCR4 está asociada a la progresión tumoral, invasión y resistencia al tratamiento. En el linfoma difuso de células grandes (LDCG) la sobreexpresión de CXCR4 concede un peor pronóstico, pero la relevancia biológica de este receptor no se ha estudiado en profundidad. En esta tesis se ha evaluado un nuevo inhibidor de CXCR4 (IQS-01.01) en modelos preclínicos de LDCG. Usando tanto modelos in vitro como in vivo de LDCG se ha concluido 1) que la inhibición de CXCR4 en LDCG tiene un efecto antitumoral, 2) que IQS-01.01RS tiene mayores propiedades farmacológicas que el inhibidor de referencia, AMD3100 3) que el tratamiento con IQS-01.01RS reduce los niveles del oncogén MYC y 4) que la combinación de IQS-01.01 RS con el inhibido de BET, CPI203, confiere un efecto antitumoral sinérgico. Los resultados de esta tesis doctoral ponen en evidencia una cooperación entre MYC y CXCR4 en LDCG e indican que la inhibición de CXCR4 en combinación con un inhibidor de MYC es una terapia prometedora contra el LDCG.