Synthesis, In Silico Designing, Microbiological Evaluation and Structure Activity Relationship of Novel Amide Derivatives of 1-(2,4-Dinitrophenyl)-2-(3-Methylbenzo[b]Thiophen-6-yl)-1H-Benzo[d]Imidazole-5-Carboxylic Acid

Abstract

Background

Due to the growing crisis of antibiotic resistance, ample of different antibiotics accessible is declining and there are only a few of new antibiotics in the drug discovery pipeline. Therefore, there is an imperative need for the progress of new antimicrobial drugs.

Method

In the present study, synthesized amide derivatives of 1-(2,4-dinitrophenyl)-2-(3-methylbenzo[b]thiophen-6-yl)-1H-benzo[d]imidazole-5-carboxylic acid by centralize the tyrosyl-tRNA synthetase and aminoacyl-tRNA synthetase (AaRS)enzymes and inhibition study by docking leads to antimicrobial activity. Molecular docking studies were conceded out on a designed amide library, and the best 23 focused amide compounds of 1-(2,4-dinitrophenyl)-2-(3-methylbenzo[b]thiophen-6-yl)-1H-benzo[d]imidazole-5-carboxylic acid were privileged for synthesis based on the dock score evaluated by Schrodinger’s maestro package and AutoDock Vina 4.2 docking software against crystal structure of enzymes (PDB ID: 1wny.PDBQT and1jil.PDBQT) and investigated for in vitro antimicrobial activity.

Results

Among the library, the best compound A-4, A-5 and A-23 showing excellent dock score by AutoDock Vina/Schrodinger’s maestro against 1wny.PDBQT:1jil.PDBQT is −9.2:–10.6/–5.402: –5.653, −9.2: –10.6/–5.526/–5.734, −9.2: –10.6/–5.183: −5.679 as compared to standard drug dock score −10.2: –10.6/–5.847: –5.895 Derivatives A-4, A-5 and A-23 also flourished good MIC against six representative microorganisms as compared to standard by tube dilution method.

Conclusions

In vitro outcome naked that new synthesized compounds having excellent antimicrobial activity can be accustomed for in vivo studies for future.

Keywords:

• Antimicrobial activity
• benzimidazole
• molecular docking
• 1wny.PDBQT
• 1jil.PDBQT

Acknowledgements

The authors are extremely pleased to the Head, DOPSNP, CUOP, Bathinda for providing vital amenities to complete this research study. The authors are also pleased to Dr. Vinod Devaraji (Application Scientist Schrödinger LLC) for his support to carry out the computational work.

Ethics approval and consent to participate

Not applicable.

Human and animal rights

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors affirm no conflict of interest, financial or otherwise.