Design, Synthesis and Antitubercular Evaluation of New Benzimidazole Scaffolds

Abstract

Background: To overcome one of the resistance mechanisms of Isoniazid (INH), there is a need of antitubercular agent that can inhibit InhA enzyme by circumvents the formation of INH-NAD+ adduct. Objective: The objective of the study is the development of novel antitubercular agents that targets Mycobacterium tuberculosis InhA (Enoyl Acyl Carrier Protein Reductase). Methods: A small molecule chemical library was used for identification of the novel InhA inhibitors using primary screening and molecular docking studies followed by scaffold hopping approach. The designed molecules, 2-(2-(hydroxymethyl)-1H- benzo[d] imidazole-1-yl)- N- substituted acetamides were synthesized by reacting (1H- benzo[d]imidazole -2-yl)methanol with appropriate 2-chloro-N-substituted acetamides / dialkylamino carbonyl chlorides respectively in good yields (42-65%). The antitubercular activity of synthesized compounds was determined by Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis H37Rv strain. The selected compounds were screened for cytotoxicity on normal cell lines. Results: The antitubercular activity data revealed that the 4-chlorophenyl substituted derivative (3b) showed good MIC value at 6.25 µg/mL and, dimethylacetamide substituted derivative (3i) showed MIC at 25 µg/mL among the tested compounds. The substitution of dimethyl acetamide (3i) group on 1st position of benzimidazole has good antitubercular activity (25µg/mL) in comparison to the diethyl acetamide group (3j, 100µg/mL). Conclusion: The antitubercular activity data indicated that the tested compounds exhibited well to moderate inhibition of the H37Rv strains. The compounds (3b) with electronegative substitution on the phenyl moiety exhibited better antitubercular activity than that of the other substitutions. The active compounds have displayed good safety profile on normal cell lines.

The Influence of the Kappa-Casein Genotype on the Nutritional Value of Milk

“…Биотехнологияның соңғы жетістіктері ДНҚ деңгейінде көптеген генетикалық полиморфизмдерді ашуға мүмкіндік берді. Нәтижесінде зерттеушілер мен ғалымдарға оларды байқалған фенотиптік вариацияның генетикалық негізін бағалау үшін маркерлер ретінде пайдалануға ұсынылды [5].…”