Synthesis, biological evaluation and computational study of novel isoniazid containing 4H-Pyrimido[2,1-b]benzothiazoles derivatives
| Autor: | Himanshu A. Pandya, Divya J. Jethava, Edwin A. Pithawala, Manoj N. Bhoi, Mayuri A. Borad, Prachi T. Acharya, Chirag N. Patel, Hitesh D. Patel |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Antitubercular Agents
Microbial Sensitivity Tests Molecular Dynamics Simulation Ligands 01 natural sciences 03 medical and health sciences Molecular dynamics Drug Discovery Coenzyme A Ligases medicine Isoniazid Molecule Benzothiazoles 030304 developmental biology Pharmacology chemistry.chemical_classification 0303 health sciences biology 010405 organic chemistry INHA Organic Chemistry Active site General Medicine Mycobacterium tuberculosis Carbon-13 NMR Combinatorial chemistry 0104 chemical sciences Molecular Docking Simulation Enzyme Pyrimidines chemistry biology.protein Proton NMR medicine.drug Protein Binding |
| Zdroj: | European journal of medicinal chemistry. 177 |
| ISSN: | 1768-3254 |
| Popis: | Synthesis of novel and potent hit molecules has an eternal demand. It is our continuous study to search novel bioactive hit molecules and as a part of this, a series of novel N′-isonicotinoyl-2-methyl-4-(pyridin-2-yl)-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carbohydrazide analogs (5a-5n) were synthesized with good yields by the conventional method. The various novel compounds have been characterized and identified by many analytical technique such as IR, 1H NMR, 13C NMR, mass spectral analysis, and elemental analysis. All the synthetic analogs (5a-5n) are evaluated for their in vitro antibacterial and anti-mycobacterial activities against different bacterial strains. Molecular docking and Molecular dynamics studies were helped in revealing the mode of action of these compounds through their interactions with the active site of the Mycobacterium tuberculosis enoyl reductase (InhA) enzyme. The calculated ADMET descriptors for the synthesized compounds validated good pharmacokinetic properties, confirming that these compounds could be used as templates for the development of new Anti-mycobacterial agents. |
| Databáze: | OpenAIRE |
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