Design, synthesis and in silico study of pyridine based 1,3,4-oxadiazole embedded hydrazinecarbothioamide derivatives as potent anti-tubercular agent
| Autor: | Rajesh N. Gacche, Rohan J. Meshram, Shuddhodan N. Kadam, Madhav J. Hebade, Sonali S. Kamble, Ajay N. Ambhore, Rahul D. Kamble, Milind V. Gaikwad, Bhaskar S. Dawane, Shrikant V. Hese |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Thiosemicarbazones Pyridines media_common.quotation_subject In silico Antitubercular Agents Oxadiazole Drug resistance Microbial Sensitivity Tests Biochemistry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship 0302 clinical medicine Structural Biology Catalytic Domain Isoniazid media_common Oxadiazoles biology Molecular Structure Chemistry Organic Chemistry Active site Free Radical Scavengers Mycobacterium tuberculosis Combinatorial chemistry Molecular Docking Simulation Computational Mathematics 030104 developmental biology Docking (molecular) 030220 oncology & carcinogenesis Drug Design Cytochrome P450 Family 51 biology.protein Pharmacophore Antitubercular Agent Rifampin Protein Binding |
| Zdroj: | Computational biology and chemistry. 80 |
| ISSN: | 1476-928X |
| Popis: | Development of novel, safe and effective drug candidates combating the emerging drug resistance has remained a major focus in the mainstream of anti-tuberculosis research. Here, we inspired to design and synthesize series of new pyridin-4-yl-1,3,4-oxadiazol-2-yl-thio-ethylidene-hydrazinecarbothioamide derivatives as potential anti-tubercular agents. The anti-tubercular bioactive assay demonstrated that the synthesized compounds exhibit potent anti-tubercular activity (MIC = 3.9–7.81 μg/mL) in comparison with reference drugs Rifampicin and Isoniazid.We employed pharmacophore probing approach for the identification of CYP51 as a possible drug target for the synthesized compounds. To understand the preferable binding mode, the synthesized molecules were docked onto the active site of Sterol 14 α-demethylases (CYP51) target. From the binding free energy of the docking results it was revealed that the compounds were effective CYP51 inhibitors and acts as antitubercular agent. |
| Databáze: | OpenAIRE |
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