The structure–antituberculosis activity relationships study in a series of 5-aryl-2-thio-1,3,4-oxadiazole derivatives
| Autor: | Nathaly Shvets, Athina Geronikaki, Anatholy Dimoglo, Robert C. Reynolds, Serghei Pogrebnoi, Fliur Macaev, Veaceslav Boldescu, Zinaida Ribkovskaia, Ghenadie Rusu |
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| Rok vydání: | 2011 |
| Předmět: |
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Molecular Oxadiazoles Stereochemistry Aryl Organic Chemistry Clinical Biochemistry Antitubercular Agents Molecular Conformation Pharmaceutical Science Thio Mycobacterium tuberculosis Biochemistry Structure-Activity Relationship chemistry.chemical_compound chemistry Catalytic Domain Drug Discovery Mycobacterium tuberculosis H37Rv Humans Molecular Medicine Molecule 1 3 4 oxadiazole derivatives Molecular Biology |
| Zdroj: | Bioorganic & Medicinal Chemistry. 19:6792-6807 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2011.09.038 |
| Popis: | A series of 82 5-aryl-2-thio-1,3,4-oxadiazole derivatives were screened for their anti-mycobacterial activities against Mycobacterium tuberculosis H37Rv. The synthesized compounds 30–37 appeared to be the most active derivatives exhibiting more than 90% inhibition of mycobacterial growth at 12.5 μg/mL. Structure–activity relationships study was performed for the given series by using the electronic-topological method combined with neural networks (ETM–NN). A system for the anti-mycobacterial activity prediction was developed as the result of training associative neural network (ASNN) with weights calculated from projections of a compound and each pharmacophoric fragment found on the elements of the Kohonen’s self-organizing maps (SOMs). From the detailed analysis of all compounds under study, the necessary requirements for a compound to possess antituberculosis activity have been formulated. The analysis has shown that any requirement’s violation for a molecule implies a considerable decrease or even complete loss of its activity. Molecular docking studies of the compounds allowed shedding light on the binding mode of these novel anti-mycobacterial inhibitors. |
| Databáze: | OpenAIRE |
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