DESIGN, SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF NOVEL BENZIMIDAZOLE, PYRIDINE AND OXADIAZOLE DERIVATIVES AS ANTITUBERCULAR AGENTS AGAINST MYCOBACTERIAL TARGET ENZYME INH A
Ayyadurai Jerad Suresh*, Jesu Robert Dilton, Sundaraiah Suresh Kumar, Durga Rjendran , Parakkot Ramakrishnan Surya
Tuberculosis is the communicable disease. InhA the enoyl-ACP reductase in Mycobacterium tuberculosis is an attractive target. Benzimidazole, Oxadiazoles and Pyridine derivatives exhibit pharmacological activities such as antimicrobial, antiviral, anticancer, anti-inflammatory, analgesic, etc. Hence decided to develop novel Benzimidazole, Oxadiazoles and Pyridine derivatives as potent anti-tubercular agents against InhA enzyme (Enoyl acyl carrier protein reductase).Compounds were designed and docked against inh A enzyme by using online docking Software Argus lab 4.0.1®. The molecules screened for best docking score and protein interaction. The selected molecules were synthesized in good yield by simple reflux condensation. Synthesized compounds were purified and characterized and biologically evaluated for their Anti tubercular activity by Microplate Alamar Blue Assay (MABA techenique). The research work concludes that the synthesized anti-tubercular molecules effectively inhibit target enzyme Enoyl acyl carrier protein reductase (inh A). The benzimidazole derivatives were active at concentrations of 1.6mcg/ml “b” and 3.125mcg/ml “a”. The synthesized pyridine derivatives “c” and “d” showed good anti tubercular activity at 1.6mcg/ml. whereas oxadiazole derivatives “ e” and “f “were active at 1.6mcg/ml. Further structural modifications of the synthesized compounds will aid in the development of potential anti tubercular molecule. The cytotoxic evaluation of all the synthesized compounds was performed. The IC50 for Rifampicin is 113 μg/ml on vero cell line. Two compounds “a” and “b” shows decreased IC50 values of 37.63 and 111.2 μg/ml. Compounds “c” and “d “ showed increased IC50 values 389.7 and 319.3. Compounds “e” and “f” also showed increased IC50 values of 299.3 and 520.
Keywords: Mycobacterium tuberculosis; MABA; Oxadiazole; Benzimidazole; Rifampicin.
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