Zeitschriftenartikel: „Biologically potent molecules“

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Fotopoulos, Ioannis, und Dimitra Hadjipavlou-Litina. „Hybrids of Coumarin Derivatives as Potent and Multifunctional Bioactive Agents: A Review“. Medicinal Chemistry 16, Nr. 3 (17.04.2020): 272–306. http://dx.doi.org/10.2174/1573406415666190416121448.

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Background: Coumarins exhibit a plethora of biological activities, e.g. antiinflammatory and anti-tumor. Molecular hybridization technique has been implemented in the design of novel coumarin hybrids with several bioactive groups in order to obtain molecules with better pharmacological activity and improved pharmacokinetic profile. Objective: Therefore, we tried to gather as many as possible biologically active coumarin hybrids referred in the literature till now, to delineate the structural characteristics in relation to the activities and to have a survey that might help the medicinal chemists to design new coumarin hybrids with drug-likeness and varied bioactivities. Results: The biological activities of the hybrids in most of the cases were found to be different from the biological activities presented by the parent coumarins. The results showed that the hybrid molecules are more potent compared to the standard drugs used in the evaluation experiments. Conclusion: Conjugation of coumarin with varied pharmacophore groups/druglike molecules responsible for different biological activities led to many novel hybrid molecules, with a multitarget behavior and improved pharmacokinetic properties.

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Thorat, Sagar S., und Ravindar Kontham. „Strategies for the synthesis of furo-pyranones and their application in the total synthesis of related natural products“. Organic Chemistry Frontiers 8, Nr. 9 (2021): 2110–62. http://dx.doi.org/10.1039/d0qo01421d.

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The furo-pyranone framework is widely present in the molecular structure of various biologically potent natural products and un-natural small molecules, and it represents a valuable target in synthetic organic chemistry and medicinal chemistry.

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Karageorgis, George, und Herbert Waldmann. „Guided by Evolution: Biology-Oriented Synthesis of Bioactive Compound Classes“. Synthesis 51, Nr. 01 (11.10.2018): 55–66. http://dx.doi.org/10.1055/s-0037-1610368.

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Biology-oriented-synthesis (BIOS), is a chemocentric approach to identifying structurally novel molecules as tools for chemical biology and medicinal chemistry research. The vast chemical space cannot be exhaustively covered by synthetic chemistry. Thus, methods which reveal biologically relevant portions of chemical space are of high value. Guided by structural conservation in the evolution of both proteins and natural products, BIOS classifies bioactive compound classes in a hierarchical manner based on molecular architecture and bioactivity. Biologically relevant scaffolds inspire and guide the synthesis of BIOS libraries, which calls for the development of suitable synthetic methodologies. These compound collections have enriched biological relevance, leading to the discovery of bioactive small molecules. These potent and selective modulators allow the study of complex biological pathways and may serve as starting points for drug discovery programs. Thus, BIOS can also be regarded as a hypothesis-generating tool, guiding the design and preparation of novel, bioactive molecular scaffolds. This review elaborates the principles of BIOS and highlights selected examples of their application, which have in turn created future opportunities for the expansion of BIOS and its combination with fragment-based compound discovery for the identification of biologically relevant small molecules with unprecedented molecular scaffolds.1 Introduction2 Structural Classification of Natural Products3 Implications and Opportunities for Biology-Oriented Synthesis4 Applications of Biology-Oriented Synthesis4.1 Chemical Structure and Bioactivity Guided Approaches4.2 Natural-Product-Derived Fragment-Based Approaches5 Conclusions and Outlook

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Wavhal, Kamalakar Kailash, und Deepak Manik Nagrik. „Synthesis of Biologically Potent α-Aminophosphonates Derivatives by Nano-Catalyst“. Oriental Journal Of Chemistry 38, Nr. 5 (31.10.2022): 1314–19. http://dx.doi.org/10.13005/ojc/380532.

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α-Aminophosphonate and their derivatives are biologically potent and have received considerable attention in a recent research scenario. The main reason is that they show triguing biological activity. α-Aminophosphonate derivatives are gaining a lot of importance in medicinal chemistry due to their application as enzyme inhibitors, herbicides, antibiotics, pharmaceutical agents and inhibitors of Excitatory Post-Synaptic Potential(EPSP) synthesis, and HIV Protease. It is also important in ati-cancer, anti-HIV, antithrombotic and antibacterial, antioxidant activity. Unfortunately, these compounds have certain limitation such as extraction, purification, of bioactive molecule and their minimum yields. For this reason, many scientists have been orienting their research towards the synthesis of molecules as a new tool to overcome this problems he prime focus of this work is the combination of three reactant derivative of benzaldehyde derivative of aniline, and diethyl phosphonate to form α-aminophosphonates derivatives by multicomponent reaction(KFR). The novel nano-catalyst i.e. polyanilinedoped with manganese (PAni-Mn) was prepared. The catalyst shows excellent catalytic activity, high yields, short reaction times, easy synthesis. The PAni was fully characterized by X-ray diffraction, TEM, SEM, and FT-IR technique.

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Naveen, Naveen, Ram Kumar Tittal, Pinki Yadav, Kashmiri Lal, Ghule Vikas D. und Ashwani Kumar. „Synthesis, molecular docking and DFT studies on biologically active 1,4-disubstituted-1,2,3-triazole-semicarbazone hybrid molecules“. New Journal of Chemistry 43, Nr. 21 (2019): 8052–58. http://dx.doi.org/10.1039/c9nj00473d.

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Biologically active semicarbazone-triazole hybrid molecules designed and synthesized from semicarbazone linked with a terminal alkyne and aromatic azidesviaCu(i)-catalyzed cycloaddition reaction. The synthesized compounds exhibited potent antibacterial activities against the tested bacterial strains. Computational results are in good agreement with thein vitroantimicrobial results.

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Gazieva, Galina A., und Konstantin Chegaev. „Special Issue “Development and Synthesis of Biologically Active Compounds”“. International Journal of Molecular Sciences 25, Nr. 7 (04.04.2024): 4015. http://dx.doi.org/10.3390/ijms25074015.

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The intention of this Special Issue is to focus on new achievements in the design, preparation, and in vitro and in vivo biological evaluation of bioactive molecules that can result in the development of natural or artificial potent compounds looking for promising pharmaceuticals and agrochemicals [...]

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Mielcarek, Michal, und Mark Isalan. „Kinetin stimulates differentiation of C2C12 myoblasts“. PLOS ONE 16, Nr. 10 (13.10.2021): e0258419. http://dx.doi.org/10.1371/journal.pone.0258419.

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Kinetin or N6-furfuryladenine (K) belongs to a class of plant hormones called cytokinins, which are biologically active molecules modulating many aspects of plant growth and development. However, biological activities of cytokinins are not only limited to plants; their effects on animals have been widely reported in the literature. Here, we found that Kinetin is a potent small molecule that efficiently stimulates differentiation of C2C12 myoblasts into myotubes in vitro. The highest efficacy was achieved at 1μM and 10μM Kinetin concentrations, in both mitogen-poor and rich media. More importantly, Kinetin was able to strongly stimulate the MyoD-dependent conversion of fibroblasts into myotubes. Kinetin alone did not give rise to fibroblast conversion and required MyoD; this demonstrates that Kinetin augments the molecular repertoire of necessary key regulatory factors to facilitate MyoD-mediated myogenic differentiation. This novel Kinetin pro-myogenic function may be explained by its ability to alter intracellular calcium levels and by its potential to impact on Reactive Oxygen Species (ROS) signalling. Taken together, our findings unravel the effects of a new class of small molecules with potent pro-myogenic activities. This opens up new therapeutic avenues with potential for treating skeletal muscle diseases related to muscle aging and wasting.

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Islam, Rainul, Sumit Maji, Souparna Kabiraj, Umme Habib, Rohan Pal, Somenath Bhattacharya, Soumallya Chakraborty und Dr Arin Bhattacharjee. „Role of in silico Drug Design in Pharmaceutical Sciences“. International Journal for Research in Applied Science and Engineering Technology 10, Nr. 5 (31.05.2022): 2358–67. http://dx.doi.org/10.22214/ijraset.2022.42836.

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Abstract: In silico drug design is the study to identify, develop, analyze, optimize drugs or biologically cum pharmaceutically active compounds by using computerized software programs as well web servers. In silico drug design is commonly known as computer aided drug design or CADD in short. This technique shows a vital role in preclinical drug design and development. CADD can improve the speed of drug design. It reduces time as well as total cost of the experiments. Potent cum suitable molecules are prepared after performing in silico drug design including CADD. Various applications like confirmation generation, homology modeling, multiple sequence alignment, molecular docking study, generation of Pharmacophores, virtual screening, de novo drug design, QSAR (Quantitative structure activity relationships) study, molecular modeling, in silico ADMET (Absorption, distribution, metabolism, excretion and toxicity) prediction of CADD has been implemented to design newer molecules. The current study focuses on different strategies cum approaches through computer aided drug designing applied to find potent, efficient and safe molecules in the field of drug discovery. Keywords: CADD, drug design, molecular docking, Pharmacophores, virtual screening, de novo drug design, QSAR, molecular modeling.

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Meyer, Claire E., Cora-Ann Schoenenberger, Juan Liu, Ioana Craciun und Cornelia G. Palivan. „DNA-tethered Polymersome Clusters as Nanotheranostic Platform“. CHIMIA International Journal for Chemistry 75, Nr. 4 (28.04.2021): 296–99. http://dx.doi.org/10.2533/chimia.2021.296.

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Nanotheranostics combine the use of nanomaterials and biologically active compounds to achieve diagnosis and treatment at the same time. To date, severe limitations compromise the use of nanotheranostic systems as potent nanomaterials are often incompatible with potent biomolecules. Herein we emphasize how a novel type of polymersome clusters loaded with active molecules can be optimized to obtain an efficient nanotheranostic platform. Polymersomes loaded with enzymes and specific dyes, respectively and exposing complementary DNA strands at their external surface formed clusters by means of DNA hybridization. We describe factors at the molecular level and other conditions that need to be optimized at each step of the cluster formation to favor theranostic efficiency.

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Meena, Khem Raj, und Shamsher S. Kanwar. „Lipopeptides as the Antifungal and Antibacterial Agents: Applications in Food Safety and Therapeutics“. BioMed Research International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/473050.

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A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of theBacillusgenus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families ofBacilluslipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activities, while Surfactin has broad range of potent antibacterial activities and this has also been used as larvicidal agent. Interestingly, lipopeptides being the molecules of biological origin are environmentally acceptable.

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Sugimoto, Yuki, Francine R. Camacho, Shuo Wang, Pranatchareeya Chankhamjon, Arman Odabas, Abhishek Biswas, Philip D. Jeffrey und Mohamed S. Donia. „A metagenomic strategy for harnessing the chemical repertoire of the human microbiome“. Science 366, Nr. 6471 (03.10.2019): eaax9176. http://dx.doi.org/10.1126/science.aax9176.

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Extensive progress has been made in determining the effects of the microbiome on human physiology and disease, but the underlying molecules and mechanisms governing these effects remain largely unexplored. Here, we combine a new computational algorithm with synthetic biology to access biologically active small molecules encoded directly in human microbiome–derived metagenomic sequencing data. We discover that members of a clinically used class of molecules are widely encoded in the human microbiome and that they exert potent antibacterial activities against neighboring microbes, implying a possible role in niche competition and host defense. Our approach paves the way toward a systematic unveiling of the chemical repertoire encoded by the human microbiome and provides a generalizable platform for discovering molecular mediators of microbiome-host and microbiome-microbiome interactions.

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Megy, Simon, Stephanie Aguero, David Da Costa, Myriam Lamrayah, Morgane Berthet, Charlotte Primard, Bernard Verrier und Raphael Terreux. „Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam1CSK4 and Pam3CSK4“. Nanomaterials 10, Nr. 11 (05.11.2020): 2209. http://dx.doi.org/10.3390/nano10112209.

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Poly(lactic acid) (PLA) nanoparticles (NPs) are widely investigated due to their bioresorbable, biocompatible and low immunogen properties. Interestingly, many recent studies show that they can be efficiently used as drug delivery systems or as adjuvants to enhance vaccine efficacy. Our work focuses on the molecular mechanisms involved during the nanoprecipitation of PLA NPs from concentrated solutions of lactic acid polymeric chains, and their specific interactions with biologically relevant molecules. In this study, we evaluated the ability of a PLA-based nanoparticle drug carrier to vectorize either vitamin E or the Toll-like receptor (TLR) agonists Pam1CSK4 and Pam3CSK4, which are potent activators of the proinflammatory transcription factor NF-κB. We used dissipative particle dynamics (DPD) to simulate large systems mimicking the nanoprecipitation process for a complete NP. Our results evidenced that after the NP formation, Pam1CSK4 and Pam3CSK4 molecules end up located on the surface of the particle, interacting with the PLA chains via their fatty acid chains, whereas vitamin E molecules are buried deeper in the core of the particle. Our results allow for a better understanding of the molecular mechanisms responsible for the formation of the PLA NPs and their interactions with biological molecules located either on their surfaces or encapsulated within them. This work should allow for a rapid development of better biodegradable and safe vectorization systems with new drugs in the near future.

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Spencer, Juliet V., Kristen M. Lockridge, Peter A. Barry, Gaofeng Lin, Monica Tsang, Mark E. T. Penfold und Thomas J. Schall. „Potent Immunosuppressive Activities of Cytomegalovirus- Encoded Interleukin-10“. Journal of Virology 76, Nr. 3 (01.02.2002): 1285–92. http://dx.doi.org/10.1128/jvi.76.3.1285-1292.2002.

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ABSTRACT Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.

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Graciano, Isabela A., Alcione S. de Carvalho, Fernando de Carvalho da Silva und Vitor F. Ferreira. „1,2,3-Triazole- and Quinoline-based Hybrids with Potent Antiplasmodial Activity“. Medicinal Chemistry 18, Nr. 5 (Mai 2022): 521–35. http://dx.doi.org/10.2174/1573406418666211110143041.

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Background: Malaria is a disease causing millions of victims every year and requires new drugs, often due to parasitic strain mutations. Thus, the search for new molecules that possess antimalarial activity is constant and extremely important. However, the potential that an antimalarial drug possesses cannot be ignored, and molecular hybridization is a good strategy to design new chemical entities. Objective: This review article aims to emphasize recent advances in the biological activities of new 1,2,3-triazole- and quinoline-based hybrids and their place in the development of new biologically active substances. More specifically, it intends to present the synthetic methods that have been utilized for the syntheses of hybrid 1,2,3-triazoles with quinoline nuclei. Method: We have comprehensively and critically discussed all the information available in the literature regarding 1,2,3-triazole- and quinoline-based hybrids with potent antiplasmodial activity. Results: The quinoline nucleus has already been proven to lead to new chemical entities in the pharmaceutical market, such as drugs for the treatment of malaria and other diseases. The same can be said about the 1,2,3-triazole heterocycle, which has been shown to be a beneficial scaffold for the construction of new drugs with several activities. However, only a few triazoles have entered the pharmaceutical market as drugs. Conclusion: Many studies have been conducted to develop new substances that may circumvent the resistance developed by the parasite that causes malaria, thereby improving the therapy currently used.

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Tangara, Salia, Léo Faïon, Catherine Piveteau, Frédéric Capet, Romain Godelier, Marion Michel, Marion Flipo, Benoit Deprez, Nicolas Willand und Baptiste Villemagne. „Rapid and Efficient Access to Novel Bio-Inspired 3-Dimensional Tricyclic SpiroLactams as Privileged Structures via Meyers’ Lactamization“. Pharmaceuticals 16, Nr. 3 (08.03.2023): 413. http://dx.doi.org/10.3390/ph16030413.

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The concept of privileged structure has been used as a fruitful approach for the discovery of novel biologically active molecules. A privileged structure is defined as a semi-rigid scaffold able to display substituents in multiple spatial directions and capable of providing potent and selective ligands for different biological targets through the modification of those substituents. On average, these backbones tend to exhibit improved drug-like properties and therefore represent attractive starting points for hit-to-lead optimization programs. This article promotes the rapid, reliable, and efficient synthesis of novel, highly 3-dimensional, and easily functionalized bio-inspired tricyclic spirolactams, as well as an analysis of their drug-like properties.

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Kang, Chungwon, Soyoun Kim, Euiyeon Lee, Jeahee Ryu, Minhyeong Lee und Youngeun Kwon. „Genetically Encoded Sensor Cells for the Screening of Glucocorticoid Receptor (GR) Effectors in Herbal Extracts“. Biosensors 11, Nr. 9 (16.09.2021): 341. http://dx.doi.org/10.3390/bios11090341.

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Although in vitro sensors provide facile low-cost ways to screen for biologically active targets, their results may not accurately represent the molecular interactions in biological systems. Cell-based sensors have emerged as promising platforms to screen targets in biologically relevant environments. However, there are few examples where cell-based sensors have been practically applied for drug screening. Here, we used engineered cortisol-detecting sensor cells to screen for natural mimetics of cortisol. The sensor cells were designed to report the presence of a target through signal peptide activation and subsequent fluorescence signal translocation. The developed sensor cells were able to detect known biological targets from human-derived analytes as well as natural product extracts, such as deer antlers and ginseng. The multi-use capability and versatility to screen in different cellular environments were also demonstrated. The sensor cells were used to identify novel GR effectors from medicinal plant extracts. Our results suggest that decursin from dongquai had the GR effector function as a selective GR agonist (SEGRA), making it a potent drug candidate with anti-inflammatory activity. We demonstrated the superiority of cell-based sensing technology over in vitro screening, proving its potential for practical drug screening applications that leads to the function-based discovery of target molecules.

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Shakya, Bhushan, und Paras Nath Yadav. „Thiosemicarbazones as Potent Anticancer Agents and their Modes of Action“. Mini-Reviews in Medicinal Chemistry 20, Nr. 8 (17.05.2020): 638–61. http://dx.doi.org/10.2174/1389557519666191029130310.

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: Thiosemicarbazones (TSCs) are a class of Schiff bases usually obtained by the condensation of thiosemicarbazide with a suitable aldehyde or ketone. TSCs have been the focus of chemists and biologists due to their wide range of pharmacological effects. One of the promising areas in which these excellent metal chelators are being developed is their use against cancer. TSCs have a wide clinical antitumor spectrum with efficacy in various tumor types such as leukemia, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. To obtain better activity, different series of TSCs have been developed by modifying the heteroaromatic system in their molecules. These compounds possessed significant antineoplastic activity when the carbonyl attachment of the side chain was located at a position α to the ring nitrogen atom, whereas attachment of the side chain β or γ to the heterocyclic N atom resulted in inactive antitumor agents. In addition, replacement of the heterocyclic ring N with C also resulted in a biologically inactive compound suggesting that a conjugated N,N,S-tridentate donor set is essential for the biological activities of thiosemicarbazones. Several possible mechanisms have been implemented for the anticancer activity of thiosemicarbazones.

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Endo, Yasuyuki, Tomohiro Yoshimi und Chisato Miyaura. „Boron clusters for medicinal drug design: Selective estrogen receptor modulators bearing carborane“. Pure and Applied Chemistry 75, Nr. 9 (01.01.2003): 1197–205. http://dx.doi.org/10.1351/pac200375091197.

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The molecular shape and hydrophobicity of dicarba-closo -dodecaboranes may allow a new medical application as biologically active molecules. Recently, we have developed potent estrogen receptor (ER) agonists bearing carborane cage. The most potent compound (BE120) exhibited activity at least several times greater than that of 17 beta-estradiol in luciferase reporter gene assay and ER alpha binding. We also designed and synthesized estrogen antagonists on the basis of the structure of BE120, and we noticed the characteristic features of compound (BE360) having carborane cage and two phenols. The ER binding affinity of BE360 is comparable to that of estradiol. To examine in vivo estrogenic activity of the compound in bone, ovariectomized (OVX) mice were given BE360 or estradiol subcutaneously for 4 weeks. Treatment with BE360 at 1–30 µg/day dose-dependently restored bone loss in OVX mice to sham level without estrogenic action in uterus. These results suggest its possible application to osteoporosis as a new type of selective ER modulator.

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Goidescu, Cerasela Mihaela, und Luminița Animarie Vida-Simiti. „The apelin-APJ system in the evolution of heart failure“. Medicine and Pharmacy Reports 88, Nr. 1 (28.01.2015): 3–8. http://dx.doi.org/10.15386/cjmed-380.

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Heart failure is a chronic, progressive disease in which the overexpression of biologically active molecules and neurohomonal activation are the key factors of the evolution and natural history. The apelin-APJ system is a newly discovered molecular pathway and the RAAS counterbalance is its principal effect. The apelin is a potent inotrope, vasodilator and diuretic with crucial cardioprotective effects against angiotensin and aldosterone injuries. Intense and prolonged RAAS induces the downregulation of the apelin and its receptor at myocardial level and cancels their protection. Compared to the vasoactive agents used in the treatment of acute heart failure, exogen apelin has unique intropic and vasodilatory effects without deleterious consequences, being a promising therapeutic option.

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Singh, Amandeep, Asif Raza, Shantu Amin, Chendil Damodaran und Arun K. Sharma. „Recent Advances in the Chemistry and Therapeutic Evaluation of Naturally Occurring and Synthetic Withanolides“. Molecules 27, Nr. 3 (28.01.2022): 886. http://dx.doi.org/10.3390/molecules27030886.

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Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.

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Harshitha, B. T., J. Jayashankar, A. P. Anand, S. Sandeep, H. S. Jayanth, C. S. Karthik, P. Mallu, N. Haraprasad und N. B. Krishnamurthy. „Structural and Functional Insights of Thiazole Derivatives as Potential Anti-inflammatory Candidate: A New Contender on Chronic and Acute SARS-CoV-2 Inflammation and Inhibition of SARS-CoV-2 Proteins“. Asian Journal of Chemistry 34, Nr. 8 (2022): 1893–920. http://dx.doi.org/10.14233/ajchem.2022.23673.

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Thiazoles are notable five-membered heterocyclic rings and their moieties can be found in several biologically active compounds of natural origin, as well as synthetic molecules that possess a wide range of pharmacological activities. Inflammation is the common cause that is associated with different disorders and diseases such as psoriasis, arthritis, infections, asthma, cancer, etc. In this article, the synthesis pattern of these novel molecules are discussed and their anti-inflammatory activities against cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) were reviewed and documented. The potent 26 thiazole analogs were validated with molecular docking against main protease (6LU7) and spike binding domain ACE2 receptor (6M0J) to defeat from the COVID-19 infections. Among this, THI-9a showed excellent binding energy and affinity against deadly SAR CoV-2. The reviewed and theoretical study information strongly suggested that thiazole derivatives can be used for the development of futuristic target drugs against death-causing diseases like SAR-CoV-2.

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Fatima, Shehnaz, Payal Gupta, Shilpa Sharma, Ashish Sharma und Subhash M. Agarwal. „ADMET profiling of geographically diverse phytochemical using chemoinformatic tools“. Future Medicinal Chemistry 12, Nr. 1 (Januar 2020): 69–87. http://dx.doi.org/10.4155/fmc-2019-0206.

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Aim: Phytocompounds are important due to their uniqueness, however, only few reach the development phase due to their poor pharmacokinetics. Therefore, preassessing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties is essential in drug discovery. Methodology: Biologically diverse databases (Phytochemica, SerpentinaDB, SANCDB and NuBBEDB) covering the region of India, Brazil and South Africa were considered to predict the ADMET using chemoinformatic tools (Qikprop, pkCSM and DataWarrior). Results: Screening through each of pharmacokinetic criteria resulted in identification of 24 compounds that adhere to all the ADMET properties. Furthermore, assessment revealed that five have potent anticancer biological activity against cancer cell lines. Conclusion: We have established an open-access database (ADMET-BIS) to enable identification of promising molecules that follow ADMET properties and can be considered for drug development.

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Changmai, Bishwajit, Gunindra Pathak, Jasha Momo H. Anal und Lalthazuala Rokhum. „Heterogeneous System in Organic Synthesis: A Review“. Mini-Reviews in Organic Chemistry 17, Nr. 6 (24.08.2020): 740–53. http://dx.doi.org/10.2174/1570193x16666190830101802.

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Due to its inherent advantages such as easy recovery and reuse of the catalysts/ reagents, and environmentally friendly nature, the heterogeneous system has gain popularity in the realm of organic synthesis. In recent years, several chemically or biologically potent molecules are achieved through heterogeneous synthesis strategies. By recalling some of the classical fundamentals of the heterogeneous system in important organic synthesis, this mini-review outlines the recent developments in the applications heterogeneous catalysts and reagents; particularly in the solid phase synthesis, esterification and transesterification reactions to produce biodiesel, and Henry reaction.

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Hari, Swetha, Toreshettahally R. Swaroop, Habbanakuppe D. Preetham, Chakrabhavi D. Mohan, Umashakara Muddegowda, Salundi Basappa, Israel Vlodavsky, Gautam Sethi und Kanchugarakoppal S. Rangappa. „Synthesis, Cytotoxic and Heparanase Inhibition Studies of 5-oxo-1-arylpyrrolidine-3- carboxamides of Hydrazides and 4-amino-5-aryl-4H-1,2,4-triazole-3-thiol“. Current Organic Synthesis 17, Nr. 3 (09.06.2020): 243–50. http://dx.doi.org/10.2174/1570179417666200225123329.

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Design of chemically novel, biologically potent small heterocyclic molecules with anticancer activities, which targets the enzyme heparanase has gained prominent clinical interest. We have synthesized a novel class of carboxamide derivatives by coupling various substituted aromatic acid hydrazides and triazoleamine with pyrrolidine carboxylic acid by using coupling agents. The synthesized compounds are characterized by spectroscopic techniques such as FT-IR, HRMS and NMR. These compounds are investigated for cytotoxicity on different cancer cell lines and heparanase inhibitory activity. Most of them showed moderate heparanase inhibitory activity and good cytotoxicity.

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Kumar, Suresh, Bhavna Saroha, Gourav Kumar, Ekta Lathwal, Sanjeev Kumar, Badri Parshad, Meena Kumari, Naveen Kumar, Mabel M. Mphahlele-Makgwane und Peter R. Makgwane. „Recent Developments in Nanocatalyzed Green Synthetic Protocols of Biologically Potent Diverse O-Heterocycles—A Review“. Catalysts 12, Nr. 6 (15.06.2022): 657. http://dx.doi.org/10.3390/catal12060657.

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The dynamic growth in green organic synthetic methodologies for diverse heterocyclic scaffolds has substantially contributed to the field of medicinal chemistry over the last few decades. The use of hybrid metal nanocatalysts (NCs) is one such benign strategy for ensuring the advancement of modern synthetic chemistry by adhering to the principles of green chemistry, which call for a sustainable catalytic system that converts reacting species into profitable chemicals at a faster rate and tends to reduce waste generation. The metal nanoparticles (NPs) enhance the exposed surface area of the catalytic active sites, thereby making it easier for reactants and metal NCs to have an effective interaction. Several review articles have been published on the preparation of metal NCs and their uses for various catalytic heterocyclic transformations. This review will summarize different metal NCs for the efficient green synthesis of various O-heterocycles. Furthermore, the review will provide a concise overview of the role of metal NCs in the synthesis of O-heterocycles and will be extremely useful to researchers working on developing novel green and simple synthetic pathways to various O-heterocyclic-derived molecules.

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Bullock, George, Joss Atkinson, Piergiorgio Gentile, Paul Hatton und Cheryl Miller. „Osteogenic Peptides and Attachment Methods Determine Tissue Regeneration in Modified Bone Graft Substitutes“. Journal of Functional Biomaterials 12, Nr. 2 (31.03.2021): 22. http://dx.doi.org/10.3390/jfb12020022.

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The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides has the potential to overcome these problems and provide a cost-effective, safe route for the manufacture of enhanced bone graft substitutes. This review considers the design of peptide-enhanced bone graft substitutes, and how peptide selection and attachment method determine clinical efficacy. It was determined that covalent attachment may reduce the known risks associated with growth factor-loaded bone graft substitutes, providing a predictable tissue response and greater clinical efficacy. Peptide choice was found to be critical, but even within recognised families of biologically active peptides, the configurations that appeared to most closely mimic the biological molecules involved in natural bone healing processes were most potent. It was concluded that rational, evidence-based design of peptide-enhanced bone graft substitutes offers a pathway to clinical maturity in this highly promising field.

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Andrianov, A. M., K. V. Furs, A. V. Gonchar, L. H. Aslanyan und A. V. Tuzikov. „Application of Virtual Screening and Molecular Modeling Technologies to Identify Potential SARS-CoV-2 Main Protease Inhibitors“. Mathematical Biology and Bioinformatics 18, Nr. 1 (22.02.2023): 15–32. http://dx.doi.org/10.17537/2023.18.15.

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A virtual screening of the molecular library of biologically active compounds was carried out to identify potential inhibitors of SARS-CoV-2 main protease (Mpro) which plays an important role in the process of virus replication. Using molecular docking and molecular dynamics, the binding energy of these compounds to the catalytic site of the enzyme was assessed, resulting in six molecules that exhibited high chemical affinity for SARS-CoV-2 Mpro. This is evidenced by the low values of the binding free energy of the ligand/Mpro complexes comparable with those predicted for the potent non-covalent SARS-CoV-2 Mpro inhibitor using the identical computational protocol. Based on the data obtained, it was concluded that the identified compounds have a good therapeutic potential for inhibiting the catalytic activity of the enzyme and form promising basic structures for the development of new effective drugs against COVID-19.

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Majee, Suman, Shilpa, Mansi Sarav, Bimal Krishna Banik und Devalina Ray. „Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities“. Pharmaceuticals 16, Nr. 6 (13.06.2023): 873. http://dx.doi.org/10.3390/ph16060873.

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N-heterocyclic scaffolds represent a privileged architecture in the process of drug design and development. It has widespread occurrence in synthetic and natural products, either those that are established or progressing as potent drug candidates. Additionally, numerous novel N-heterocyclic analogues with remarkable physiological significance and extended pharmaceutical applications are escalating progressively. Hence, the classical synthetic protocols need to be improvised according to modern requirements for efficient and eco-friendly approaches. Numerous methodologies and technologies emerged to address the green and sustainable production of various pharmaceutically and medicinally important N-heterocyclic compounds in last few years. In this context, the current review unveils greener alternatives for direct access to categorically differentiated N-heterocyclic derivatives and its application in the establishment of biologically active potent molecules for drug design. The green and sustainable methods accentuated in this review includes microwave-assisted reactions, solvent-free approaches, heterogeneous catalysis, ultrasound reactions, and biocatalysis.

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Mathew, Neal D., David I. Schlipalius und Paul R. Ebert. „Sulfurous Gases As Biological Messengers and Toxins: Comparative Genetics of Their Metabolism in Model Organisms“. Journal of Toxicology 2011 (2011): 1–14. http://dx.doi.org/10.1155/2011/394970.

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Gasotransmitters are biologically produced gaseous signalling molecules. As gases with potent biological activities, they are toxic as air pollutants, and the sulfurous compounds are used as fumigants. Most investigations focus on medical aspects of gasotransmitter biology rather than toxicity toward invertebrate pests of agriculture. In fact, the pathways for the metabolism of sulfur containing gases in lower organisms have not yet been described. To address this deficit, we use protein sequences fromHomo sapiensto query Genbank for homologous proteins inCaenorhabditis elegans,Drosophila melanogaster, andSaccharomyces cerevisiae. InC. elegans, we find genes for all mammalian pathways for synthesis and catabolism of the three sulfur containing gasotransmitters, H2S, SO2and COS. The genes for H2S synthesis have actually increased in number inC. elegans. Interestingly,D. melanogasterand Arthropoda in general, lack a gene for 3-mercaptopyruvate sulfurtransferase, an enzym for H2S synthesis under reducing conditions.

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Hernández-López, Hiram, Christian Jairo Tejada-Rodríguez und Socorro Leyva-Ramos. „A Panoramic Review of Benzimidazole Derivatives and their Potential Biological Activity“. Mini-Reviews in Medicinal Chemistry 22, Nr. 9 (Mai 2022): 1268–80. http://dx.doi.org/10.2174/1389557522666220104150051.

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Abstract: The therapeutic potential of the benzimidazole nucleus has been recognized since 1944, and it is an important heterocycle system due to its presence in a wide range of bioactive compounds such as antiviral, anticancer, antibacterial, and so on, where optimization of substituents in this class of pharmacophore has resulted in many drugs. Its broad biological activity stems from physicochemical properties such as hydrogen bond donor-acceptor capability, π→π stacking interactions, coordination bonds with metals as ligands and hydrophobic interactions; properties that allow them to easily bind with a series of biomolecules, including enzymes and nucleic acids, causing a growing interest in these types of molecules. This review aims to present an overview to leading benzimidazole derivatives, as well as to show the importance of the nature and type of substituents at the N1, C2, and C5(6) positions when they are biologically evaluated, which can lead to obtaining potent drug candidate with a significant range of biological activities.

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Joshi, Rekha R., Jay Z. Chandanshive und Pradip D. Lokhande. „Ammonium Chloride Promoted One-Pot, Three-Component Mannich Reaction: An Efficient Synthesis of β-Amino Ketones and β-Amino Esters“. Asian Journal of Chemistry 34, Nr. 12 (2022): 3353–60. http://dx.doi.org/10.14233/ajchem.2022.23978.

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Ammonium chloride was found to efficiently reagent for the one pot-three component Mannich reaction between aromatic aldehyde, ketone and amine in ethanol at room temperature to furnish β-amino ketones in good to excellent yields. The said protocol was further applied for the direct synthesis of β-amino esters, which are important precursors for the synthesis of β-amino acids. This protocol is potentially applicable for the development of a clean and environment-friendly strategy for the synthesis of β-amino ketones and found applications in the synthesis of potent biologically active molecules due to its simple experimental conditions, inexpensive reagents and straight forward product isolation procedure.

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Jin, Hyun Yong, Yanyan Tudor, Kaylee Choi, Zhifei Shao, Brian A. Sparling, Joseph G. McGivern und Antony Symons. „High-Throughput Implementation of the NanoBRET Target Engagement Intracellular Kinase Assay to Reveal Differential Compound Engagement by SIK2/3 Isoforms“. SLAS DISCOVERY: Advancing the Science of Drug Discovery 25, Nr. 2 (18.12.2019): 215–22. http://dx.doi.org/10.1177/2472555219893277.

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The real-time quantification of target engagement (TE) by small-molecule ligands in living cells remains technically challenging. Systematic quantification of such interactions in a high-throughput setting holds promise for identification of target-specific, potent small molecules within a pathophysiological and biologically relevant cellular context. The salt-inducible kinases (SIKs) belong to a subfamily of the AMP-activated protein kinase (AMPK) family and are composed of three isoforms in humans (SIK1, SIK2, and SIK3). They modulate the production of pro- and anti-inflammatory cytokines in immune cells. Although pan-SIK inhibitors are sufficient to reverse SIK-dependent inflammatory responses, the apparent toxicity associated with SIK3 inhibition suggests that isoform-specific inhibition is required to realize therapeutic benefit with acceptable safety margins. Here, we used the NanoBRET TE intracellular kinase assay, a sensitive energy transfer technique, to directly measure molecular proximity and quantify TE in HEK293T cells overexpressing SIK2 or SIK3. Our 384-well high-throughput screening of 530 compounds demonstrates that the NanoBRET TE intracellular kinase assay was sensitive and robust enough to reveal differential engagement of candidate compounds with the two SIK isoforms and further highlights the feasibility of high-throughput implementation of NanoBRET TE intracellular kinase assays for target-driven small-molecule screening.

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Proaño-Bolaños, Carolina, Ailín Blasco-Zúñiga, José Rafael Almeida, Lei Wang, Miguel Angel Llumiquinga, Miryan Rivera, Mei Zhou, Tianbao Chen und Chris Shaw. „Unravelling the Skin Secretion Peptides of the Gliding Leaf Frog, Agalychnis spurrelli (Hylidae)“. Biomolecules 9, Nr. 11 (30.10.2019): 667. http://dx.doi.org/10.3390/biom9110667.

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Frog skin secretions contain medically-valuable molecules, which are useful for the discovery of new biopharmaceuticals. The peptide profile of the skin secretion of Agalychnis spurrelli has not been investigated; therefore, the structural and biological characterization of its compounds signify an inestimable opportunity to acquire new biologically-active chemical scaffolds. In this work, skin secretion from this amphibian was analysed by molecular cloning and tandem mass spectrometry. Although the extent of this work was not exhaustive, eleven skin secretion peptides belonging to five peptide families were identified. Among these, we report the occurrence of two phyllokinins, and one medusin-SP which were previously reported in other related species. In addition, eight novel peptides were identified, including four dermaseptins, DRS-SP2 to DRS-SP5, one phylloseptin-SP1, and three orphan peptides. Phylloseptin-SP1 and dermaseptins-SP2 were identified in HPLC fractions based on their molecular masses determined by MALDI-TOF MS. Among the antimicrobial peptides, dermaseptin-SP2 was the most potent, inhibiting Escherichia coli, Staphylococcus aureus, and ORSA with a minimum inhibitory concentration (MIC) of 2.68 μM, and Candida albicans with an MIC of 10.71 μM, without haemolytic effects. The peptides described in this study represent but a superficial glance at the considerable structural diversity of bioactive peptides produced in the skin secretion of A. spurrelli.

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Swarbrick, Joanna M., Andrew M. Riley, Stephen J. Mills und Barry V. L. Potter. „Designer small molecules to target calcium signalling“. Biochemical Society Transactions 43, Nr. 3 (01.06.2015): 417–25. http://dx.doi.org/10.1042/bst20140293.

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Synthetic compounds open up new avenues to interrogate and manipulate intracellular Ca2+ signalling pathways. They may ultimately lead to drug-like analogues to intervene in disease. Recent advances in chemical biology tools available to probe Ca2+ signalling are described, with a particular focus on those synthetic analogues from our group that have enhanced biological understanding or represent a step towards more drug-like molecules. Adenophostin (AdA) is the most potent known agonist at the inositol 1,4,5-trisphosphate receptor (IP3R) and synthetic analogues provide a binding model for receptor activation and channel opening. 2-O-Modified inositol 1,4,5-trisphosphate (IP3) derivatives that are partial agonists at the IP3R reveal key conformational changes of the receptor upon ligand binding. Biphenyl polyphosphates illustrate that simple non-inositol surrogates can be engineered to give prototype IP3R agonists or antagonists and act as templates for protein co-crystallization. Cyclic adenosine 5′-diphosphoribose (cADPR) can be selectively modified using total synthesis, generating chemically and biologically stable tools to investigate Ca2+ release via the ryanodine receptor (RyR) and to interfere with cADPR synthesis and degradation. The first neutral analogues with a synthetic pyrophosphate bioisostere surprisingly retain the ability to release Ca2+, suggesting a new route to membrane-permeant tools. Adenosine 5′-diphosphoribose (ADPR) activates the Ca2+-, Na+- and K+-permeable transient receptor potential melastatin 2 (TRPM2) cation channel. Synthetic ADPR analogues provide the first structure-activity relationship (SAR) for this emerging messenger and the first functional antagonists. An analogue based on the nicotinic acid motif of nicotinic acid adenine dinucleotide phosphate (NAADP) antagonizes NAADP-mediated Ca2+ release in vitro and is effective in vivo against induced heart arrhythmia and autoimmune disease, illustrating the therapeutic potential of targeted small molecules.

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Uemura, Daisuke, Masaki Kita, Hirokazu Arimoto und Makoto Kitamura. „Recent aspects of chemical ecology: Natural toxins, coral communities, and symbiotic relationships“. Pure and Applied Chemistry 81, Nr. 6 (05.05.2009): 1093–111. http://dx.doi.org/10.1351/pac-con-08-08-12.

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The discovery of new ecologically active compounds often triggers the development of basic scientific concepts in the field of biological sciences, since such compounds have direct physiological and behavioral effects on other living organisms. We have focused on the identification of natural key compounds that control biologically and physiologically intriguing phenomena. We describe three recent aspects of chemical ecology that we have investigated: natural toxins, coral communities, and symbiotic relationships. Blarina toxin (BLTX) is a lethal mammalian venom that was isolated from the short-tailed shrew. Duck-billed platypus venom shows potent Ca2+ influx in neuroblastoma cells. The venom of the solitary wasp contains arginine kinase-like protein and is used to paralyze its prey to feed its larva. The ecological behaviors of corals are controlled by combinations of small molecules. The polyol compound symbiodinolide may serve as a defense substance for symbiotic dinoflagellates to prevent digestion of their host animals. These compounds reveal the wonder of nature, in both terrestrial and marine ecological systems.

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Gautam, Ravi. „Synthesis of Pyrazole Derivative Incorporating Fluorine in the Aromatic Substitution for Physiological and Pharmacological Studies“. Journal of Pharmaceutical Research Science & Technology 7, Nr. 1 (30.06.2023): 1–25. http://dx.doi.org/10.31531/jprst.1000168.

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Over the past decade, drug resistance has become a growing problem in the treatment of infectious diseases caused by bacteria, fungi and viruses. In particular, resistance of bacterial pathogens to current antibiotics has emerged as a measure of health problems. This is especially true in the case of infectious diseases such as pneumonia, meningitis and tuberculosis, which would once have been easily treated with antibiotics, is no longer so readily treated. At present, all widely used antibiotic, including some of the agent such as streptogramins and new generation fluoroquinolones are subjected to bacterial resistance. The search for new antimicrobial agent is one of the most challenging tasks to the medicinal chemist. A search for new antimicrobial compounds with potent and minor toxicity continues to be a region of exploration in medicinal chemistry. It has been well recognized that nitrogen containing heterocyclic molecule is a seat of diverse medicinal activities. Heterocyclic nucleus Pyrazole constitutes an important class of compounds for new drug development. The synthesis of these derivatives and investigation of their chemical and biological behavior have gained more importance in recent decades. Owing to the pharmacological importance of Pyrazole, and its derivatives, in the present work, it has been contemplated to combine various biologically active moieties with these heterocycles through active functional systems to form new molecular framework. Prompted by the therapeutic importance of these heterocyclic derivatives, in the present research work we have synthesized Pyrazole with fluorinated aromatic rings, and its derivatives through multistep reaction. Appropriate synthetic methodologies have been developed for the synthesis of new molecules. Their purification techniques have been established. All the newly synthesized compounds have been characterized by 1H NMR, 13C NMR, mass spectral, IR and elemental analyses. Also structures of a few molecules have been confirmed by X-ray crystallographic analysis. Further, the target molecules have been evaluated for their in vitro antibacterial and antifungal activity. From the pharmacological evaluation, it has been observed that some of Pyrazole, derivatives showed good antimicrobial activity

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Swennen, D., F. Rentier-Delrue, B. Auperin, P. Prunet, G. Flik, S. E. Wendelaar Bonga, M. Lion und J. A. Martial. „Production and purification of biologically active recombinant tilapia (Oreochromis niloticus) prolactins“. Journal of Endocrinology 131, Nr. 2 (November 1991): 219—NP. http://dx.doi.org/10.1677/joe.0.1310219.

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ABSTRACT Recombinant expression vectors carrying tilapia prolactin-I or -II (tiPRL-I or tiPRL-II) cDNA were constructed and the tiPRL-I and II proteins were produced in E. coli as inclusion bodies. These inclusion bodies were dissolved in 6 mol urea/1. Refolding of the proteins was followed by SDS-PAGE under non-reducing conditions so as to visualize the oxidized state of the molecules. Proteins tiPRL-I and tiPRL-II were purified by gel filtration and ion-exchange chromatography. The N-terminal sequence and bioactivities of both purified proteins were then analysed. Recombinant tiPRL-I and tiPRL-II induced a significant rise in plasma calcium levels as well as in mucocyte density in the abdominal skin epithelium. When tested on kidney membrane, both proteins exhibited potency in competing with 125I-labelled tiPRL-I for binding sites, but tiPRL-I seemed to be more potent than tiPRL-II in competing for these sites. The results obtained for the biological activities tested suggest that both recombinant prolactins were correctly refolded and had retained the full biological activity previously observed with the natural hormone preparations extracted from the animals. Journal of Endocrinology (1991) 131, 219–227

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Sharma, Pratibha, Manjinder Singh, Varinder Singh, Thakur Gurjeet Singh, Tanveer Singh und Sheikh F. Ahmad. „Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease“. Molecules 28, Nr. 18 (12.09.2023): 6579. http://dx.doi.org/10.3390/molecules28186579.

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No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.

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Naseer, N., A. Fatima, M. T. Cheema, S. Hasnain und I. Sajid. „Evaluation of antioxidant, antimicrobial and antitumor compounds production potential of Streptomyces antioxidans PU-12M“. Research Journal of Biotechnology 17, Nr. 11 (25.10.2022): 19–28. http://dx.doi.org/10.25303/1711rjbt19028.

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Streptomycetes are prolific producers of biologically active secondary metabolites with great structural and functional diversity, which are widely used as pharmaceutical products. The strain Streptomyces sp. PU-12M was investigated for its potential to produce antioxidant, antimicrobial and antitumor compounds. For this purpose, the laboratory scale fermentation (10 liters working volume) of the strain was performed followed by cell separation, solvent extraction and partial purification of biologically active compounds by silica gel fractionation column chromatography and preparative TLC. The antioxidant activity was determined by DPPH radical scavenging assay, antimicrobial activity by agar well diffusion assay while in vitro antitumor activity was determined by MTT and SRB assays. Altogether 24 partially purified compounds or fractions were retrieved from the extract of strain Streptomyces Sp. PU-12M and were subsequently investigated for biological activity. Among them, three fractions were found to have potent antioxidant activity. The crude extracts and the partially purified fractions were found to have promising antimicrobial activity with MIC up to 3.2mg/ml. The partially purified fractions exhibited varied cytotoxicity ranging from 40% to 100% mortality against brine shrimp (Artemia salina) larvae and 22% to 67% growth inhibition of HCT 116 colorectal cancer cell lines. The study reveals that Streptomyces antioxidans PU-12M is a proliferent producer of bioactive secondary metabolites and can be exploited further to produce the commercially useful bioactive molecules.

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Yeh, Chiou-Yueh, Chun-Nan Lin, Chuan-Fa Chang, Chun-Hung Lin, Huei-Ting Lien, Jen-Yang Chen und Jean-San Chia. „C-Terminal Repeats of Clostridium difficile Toxin A Induce Production of Chemokine and Adhesion Molecules in Endothelial Cells and Promote Migration of Leukocytes“. Infection and Immunity 76, Nr. 3 (26.12.2007): 1170–78. http://dx.doi.org/10.1128/iai.01340-07.

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ABSTRACT The C-terminal repeating sequences of Clostridium difficile toxin A (designated ARU) are homologous to the carbohydrate-binding domain of streptococcal glucosyltransferases (GTFs) that were recently identified as potent modulins. To test the hypothesis that ARU might exert a similar biological activity on endothelial cells, recombinant ARU (rARU), which was noncytotoxic to cell cultures, was analyzed using human umbilical vein endothelial cells. The rARU could bind directly to endothelial cells in a serum- and calcium-dependent manner and induce the production of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein 1 in a dose-dependent manner. An oligosaccharide binding assay indicated that rARU, but not GTFC, binds preferentially to Lewis antigens and 3′HSO3-containing oligosaccharides. Binding of rARU to human endothelial or intestinal cells correlated directly with the expression of Lewis Y antigen. Bound rARU directly activated mitogen-activated protein kinases and the NF-κB signaling pathway in endothelial cells to release biologically active chemokines and adhesion molecules that promoted migration in a transwell assay and the adherence of polymorphonuclear and mononuclear cells to the endothelial cells. These results suggest that ARU may bind to multiple carbohydrate motifs to exert its biological activity on human endothelial cells.

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Irfan, Ali, Ameer Fawad Zahoor, Shagufta Kamal, Mubashir Hassan und Andrzej Kloczkowski. „Ultrasonic-Assisted Synthesis of Benzofuran Appended Oxadiazole Molecules as Tyrosinase Inhibitors: Mechanistic Approach through Enzyme Inhibition, Molecular Docking, Chemoinformatics, ADMET and Drug-Likeness Studies“. International Journal of Molecular Sciences 23, Nr. 18 (19.09.2022): 10979. http://dx.doi.org/10.3390/ijms231810979.

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Furan-oxadiazole structural hybrids belong to the most promising and biologically active classes of oxygen and nitrogen containing five member heterocycles which have expanded therapeutic scope and potential in the fields of pharmacology, medicinal chemistry and pharmaceutics. A novel series 5a–j of benzofuran-oxadiazole molecules incorporating S-alkylated amide linkage have been synthesized using ultrasonic irradiation and screened for bacterial tyrosinase inhibition activity. Most of the synthesized furan-oxadiazole structural motifs exhibited significant tyrosinase inhibition activity in the micromolar range, with one of the derivatives being more potent than the standard drug ascorbic acid. Among the tested compounds, the scaffold 5a displayed more tyrosinase inhibition efficacy IC50 (11 ± 0.25 μM) than the ascorbic acid IC50 (11.5 ± 0.1 μM). Compounds 5b, 5c and 5d efficiently inhibited bacterial tyrosinase with IC50 values in the range of 12.4 ± 0.0–15.5 ± 0.0 μM. The 2-fluorophenylacetamide containing furan-oxadiazole compound 5a may be considered as a potential lead for tyrosinase inhibition with lesser side effects as a skin whitening and malignant melanoma anticancer agent.

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Poddar, Anindita, Biplab Rajbanshi, Sukdev Majumder, Subhankar Choudhury, Ayesha Hossain und Mahendra Nath Roy. „Physico-chemical and spectroscopic study of some biologically potent molecules in aqueous solution of an anti-malarial drug molecule with reference to diverse molecular interactions simultaneously optimized by DFT“. Fluid Phase Equilibria 579 (April 2024): 114025. http://dx.doi.org/10.1016/j.fluid.2024.114025.

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Koutoulogenis, Giorgos S., und George Kokotos. „Nitro Fatty Acids (NO2-FAs): An Emerging Class of Bioactive Fatty Acids“. Molecules 26, Nr. 24 (13.12.2021): 7536. http://dx.doi.org/10.3390/molecules26247536.

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Unsaturated nitro fatty acids (NO2-FAs) constitute a category of molecules that may be formed endogenously by the reaction of unsaturated fatty acids (UFAs) with secondary species of nitrogen monoxide and nitrite anions. The warhead of NO2-FAs is a nitroalkene moiety, which is a potent Michael acceptor and can undergo nucleophilic attack from thiol groups of biologically relevant proteins, showcasing the value of these molecules regarding their therapeutic potential against many diseases. In general, NO2-FAs inhibit nuclear factorκ-B (NF-κB), and simultaneously they activate nuclear factor (erythroid derived)-like 2 (Nrf2), which activates an antioxidant signaling pathway. NO2-FAs can be synthesized not only endogenously in the organism, but in a synthetic laboratory as well, either by a step-by-step synthesis or by a direct nitration of UFAs. The step-by-step synthesis requires specific precursor compounds and is in position to afford the desired NO2-FAs with a certain position of the nitro group. On the contrary, the direct nitration of UFAs is not a selective methodology; thus, it affords a mixture of all possible nitro isomers.

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Macejova, Dana, L. Toporova und J. Brtko. „The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals“. Endocrine Regulations 50, Nr. 3 (01.07.2016): 154–64. http://dx.doi.org/10.1515/enr-2016-0018.

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Abstract Retinoic acid (RA), an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR) and rexinoid nuclear receptors (RXR), which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances. They may affect processes of reproductive system in mammals, predominantly via nuclear receptor signaling pathways. Triorganotins, such as tributyltin chloride (TBTCl) and triphenyltin chloride (TPTCl), are capable to bind to RXR molecules, and thus represent potent agonists of RXR subtypes of nuclear receptors not sharing any structural characteristics with endogenous ligands of nuclear receptors. Th is article summarizes selected effects of biologically active retinoids and rexinoids on both male and female reproduction and also deals with the effects of organotin compounds evoking endocrine disrupting actions in reproduction.

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Capon, Robert J. „Australian microbial biodiscovery: from bugs to drugs“. Microbiology Australia 31, Nr. 2 (2010): 74. http://dx.doi.org/10.1071/ma10074.

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To maintain and improve the quality of life offered by modern healthcare requires an ongoing commitment to the development of new drugs, to improve and replace those that have become less effective, and to bring to the community safer treatments for an ever-wider array of important diseases. Irrespective of the specific medical need, the drug discovery pipeline is critically dependent on access to diverse, high-quality molecular libraries capable of inspiring drug-led discovery, and ultimately new drugs. A poor choice of chemistry leads to wasted resources and no drugs. Historically the pharmaceutical industry has relied heavily on microbial natural products, which represent an extraordinarily diverse, preassembled pool of biologically active molecules, programmed to be potent and selective modulators of key biopolymers, cells, tissues, organs and animals. Knowledge of Nature?s intellectual property, gleaned from the evolutionary equivalent of a billion-year global drug discovery program, with an unlimited budget and a workforce of trillions, can disclose privileged bioactive structures that inform, guide and inspire modern drug discovery, re-purposing ecological advantage to pharmaceutical benefit.

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Melnikova, Nina B., Olga N. Solovyova und Evgeni N. Evgeni N. Kochetkov. „BIOMIMETIC APPROACHES TO STUDY OF PROPERTIES OF MEDICINAL SUBSTANCES“. IZVESTIYA VYSSHIKH UCHEBNYKH ZAVEDENII KHIMIYA KHIMICHESKAYA TEKHNOLOGIYA 62, Nr. 10 (29.10.2019): 4–29. http://dx.doi.org/10.6060/ivkkt.20196210.5917.

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The review is devoted to an assessment of the current level of use of biomimetic approaches to the study of the properties of known drugs and the development of new drugs. In this review, we consider the main biological functions of superoxide dismutase, namely the catalytic decomposition of toxic superoxide anion of oxygen to the molecular form of oxygen and protection against induced apoptosis. The biomimetic enzymes-Mn- and TEMPO-containing equivalents of superoxide dismutase SOD with antitumor and antioxidant activity were discussed more detail. The relationship between the properties and activity of SOD mimetics with their structure among them the nature of the anion and ligands, the coordination number, the geometry of the presence of conjugated bonds, and other parameters of the molecules. The study of the properties of Mn-SOD mimetics makes it possible to develop a new class of drugs successfully tested by in vivo and in vitro experiments and which are at the stages of clinical trials. Stable TEMPO radicals containing compounds are able to perform SOD functions, exhibiting antioxidant activity in relation not only to superoxide-anion, but also to peroxynitrile, and moreover to act as a spin label. The biomimetic membrane systems (monolayers, planar lipid bilayers, liposomes and other nano-sized objects) are discussed too for studying properties in in vitro experiments and for delivering potent and medicinal substances. The biomimetic approach combination allows to create the new promising drugs, including those based on SOD mimetics, and to develop the synthetic analogues of biologically active substances and methods of their delivery. The advantages of such dosage forms are lower toxicity of the preparations, lack of immunogenicity and a decrease in the dose of potent drugs.

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Ko, Ko-Chun, Binghe Wang, Phang C. Tai und Charles D. Derby. „Identification of Potent Bactericidal Compounds Produced by Escapin, an l-Amino Acid Oxidase in the Ink of the Sea Hare Aplysia californica“. Antimicrobial Agents and Chemotherapy 52, Nr. 12 (13.10.2008): 4455–62. http://dx.doi.org/10.1128/aac.01103-08.

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ABSTRACT The ink of sea hares (Aplysia californica) contains escapin, an l-amino acid oxidase that metabolizes l-lysine, thereby producing a mixture that kills microbes and deters attacking predators. This secretion contains H2O2, ammonia, and an equilibrium mixture of “escapin intermediate product” (EIP-K) that includes α-keto-ε-aminocaproic acid and several other molecules. Components of the equilibrium mixture react nonenzymatically with H2O2 to form “escapin end product” (EEP-K), which contains δ-aminovaleric acid and δ-valerolactam. The proportions of the molecules in this equilibrium mixture change with pH, and this is biologically important because the secretion is pH 5 when released but becomes pH 8 when fully diluted in seawater. The goal of the current study was to identify which molecules in this equilibrium mixture are bactericidal. We show that a mixture of H2O2 and EIP-K, but not EEP-K, at low mM concentrations is synergistically responsible for most of the bactericidal activity of the secretion against Escherichia coli, Vibrio harveyi, Staphylococcus aureus, and Pseudomonas aeruginosa. Low pH enhances the bactericidal effect, and this does not result from stress associated with low pH itself. Sequential exposure to low mM concentrations of EIP-K and H2O2, in either order, does not kill E. coli. Reaction products formed when l-arginine is substituted for l-lysine have almost no bactericidal activity. Our results favor the idea that the bactericidal activity is due to unstable intermediates of the reaction of α-keto-ε-aminocaproic acid with H2O2.

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Ferreira, Letícia Tiburcio, Joyce V. B. Borba, José Teófilo Moreira-Filho, Aline Rimoldi, Carolina Horta Andrade und Fabio Trindade Maranhão Costa. „QSAR-Based Virtual Screening of Natural Products Database for Identification of Potent Antimalarial Hits“. Biomolecules 11, Nr. 3 (19.03.2021): 459. http://dx.doi.org/10.3390/biom11030459.

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With about 400,000 annual deaths worldwide, malaria remains a public health burden in tropical and subtropical areas, especially in low-income countries. Selection of drug-resistant Plasmodium strains has driven the need to explore novel antimalarial compounds with diverse modes of action. In this context, biodiversity has been widely exploited as a resourceful channel of biologically active compounds, as exemplified by antimalarial drugs such as quinine and artemisinin, derived from natural products. Thus, combining a natural product library and quantitative structure–activity relationship (QSAR)-based virtual screening, we have prioritized genuine and derivative natural compounds with potential antimalarial activity prior to in vitro testing. Experimental validation against cultured chloroquine-sensitive and multi-drug-resistant P. falciparum strains confirmed the potent and selective activity of two sesquiterpene lactones (LDT-597 and LDT-598) identified in silico. Quantitative structure–property relationship (QSPR) models predicted absorption, distribution, metabolism, and excretion (ADME) and physiologically based pharmacokinetic (PBPK) parameters for the most promising compound, showing that it presents good physiologically based pharmacokinetic properties both in rats and humans. Altogether, the in vitro parasite growth inhibition results obtained from in silico screened compounds encourage the use of virtual screening campaigns for identification of promising natural compound-based antimalarial molecules.

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D. N. Mehta, P. H. Patel, S. D. Mandal und G. S. Chakraborthy. „In-silico APPROACH FOR VIRTUAL SCREENING AND MOLECULAR DOCKING OF FLAVONOIDS AS ERBB4 KINASE INHIBITORS IN THE TREATMENT OF CANCER“. Rasayan J. Chem 17, Nr. 02 (2024): 605–10. http://dx.doi.org/10.31788/rjc.2023.1728769.

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The ongoing anticancer treatment is resulting in resistance to treatments, less efficacy, side effects, and other issues that need to be overcome by new anticancer drugs. Focusing on novel anticancer target ErbB4 kinase, responsible for tumor growth can be a promising approach against cancer. Naturally occurring plant-derived compounds are an important source of biologically active molecules with different chemical components having very little toxicity and high efficacy. This research highlights binding affinity, drug-like properties, bioactivity and toxicity prediction, and in-silico study of various flavonoids in cancer with the help of different software. The selected flavonoids had the lowest binding affinity which is the highest docking score, stipulating that they are efficacious and potent anticancer agents. These compounds are good contenders for further experimental investigations because of their potential for bioactivity and potential drug-like qualities.

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Halambage, Upul D., Jason P. Wong, Bruce J. Melancon, Craig W. Lindsley und Christopher Aiken. „Microplate-Based Assay for Identifying Small Molecules That Bind a Specific Intersubunit Interface within the Assembled HIV-1 Capsid“. Antimicrobial Agents and Chemotherapy 59, Nr. 9 (15.06.2015): 5190–95. http://dx.doi.org/10.1128/aac.00646-15.

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ABSTRACTDespite the availability of >30 effective drugs for managing HIV-1 infection, no current therapy is curative, and long-term management is challenging owing to the emergence and spread of drug-resistant mutants. Identification of drugs against novel HIV-1 targets would expand the current treatment options and help to control resistance. The highly conserved HIV-1 capsid protein represents an attractive target because of its multiple roles in replication of the virus. However, the low antiviral potencies of the reported HIV-1 capsid–targeting inhibitors render them unattractive for therapeutic development. To facilitate the identification of more-potent HIV-1 capsid inhibitors, we developed a scintillation proximity assay to screen for small molecules that target a biologically active and specific intersubunit interface in the HIV-1 capsid. The assay, which is based on competitive displacement of a known capsid-binding small-molecule inhibitor, exhibited a signal-to-noise ratio of >9 and a Z factor of >0.8. In a pilot screen of a chemical library containing 2,400 druglike compounds, we obtained a hit rate of 1.8%. This assay has properties that are suitable for screening large compound libraries to identify novel HIV-1 capsid ligands with antiviral activity.

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