Synthesis, in-silico Designing, SAR and Microbiological Evaluation of Novel Amide Derivatives of 1-(4-Nitrophenyl)-2-(3-methylbenzo[b] thiophen-6-yl)-1H-benzo[d]imidazole-5-carboxylic Acid

Abstract:

Background: Due to this increasing predicament of antibiotic confrontation, the lot of distinct antibiotics available is dwindling and there are only smatterings of new antibiotics in the drug development channel. Therefore, an intense necessitate for new antimicrobial drugs. In current study, we have synthesized the new derivatives with the help of molecular docking studies and investigated antimicrobial activities. Methods: By focusing the enzymes i.e. aminoacyl-tRNA synthetase (AaRS) and tyrosyl-tRNA synthetase, new amides of 2-(3-methylbenzo[b]thiophen-6-yl)-1-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylic acid were synthesized and inhibition by docking study precedence to antimicrobial action. Studies were accomplished on a designed library of amide derivatives with the help of docking softwares i.e. AutoDock Vina 4.2 and Schrodinger’s maestro package against crystal structure of enzymes (PDB ID: 1wny.PDBQT and1jil.PDBQT). Based upon their dock score, superlative 23 focused amide derivatives of 2-(3-methylbenzo[b]thiophen-6-yl)- 1-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylic acid were synthesized and further investigated for in vitro antimicrobial. Results: Among the library, superlative compounds C-1, C-10 and C-19 having tremendous dock score by AutoDock Vina/Schrodinger’s maestro against 1wny.PDBQT:1jil.PDBQT-9.0:-9.9/ -5.144:-5.328,-9.2:-9.4/ -5.007:- 5.369, -9.0:-9.6/ -5.184:-5.264 as compared to standard drug dock score -10.2:- 10.6/-5.847:-5.895.C-1, C-10 and C-19 derivatives also exhibited good MIC against six representative micro-organisms as compared to standard by tube dilution method. Conclusion: In-vitro results revealed that a large number of synthesized compounds having good antimicrobial activity and dock score can be used for in vivo studies for future. In-silico studies and in vitro results comply with each other.

Key words: Benzimidazole, 1jil.PDBQT, 1wny.PDBQT, Antimicrobial Activity, SAR.