Design Synthesis In Vitro, In Silico Biological Evaluation of Novel Benzimidazole Derivatives as Antibacterial and Antifungal Agents
Shikha Sharma, Anurag Agrawal, Jagdish K. Sahu, Rishabh Khare, Mukesh K. GuptaBackground:
Drug-resistant microorganisms are a major concern, particularly as more strains develop resistance to various antimicrobial agents. Some microbes are currently immune to all antibiotics. Consequently, it is imperative to develop novel drugs that maintain their effective-ness. The benzimidazole nucleus can be found in a wide variety of heterocyclic compounds in na-ture. Numerous investigations have been conducted on the physiological effects of molecules con-taining this moiety.
Method:
Some more recent benzimidazole analogues were synthesized through the synthetic stages of o-phenylene diamine with 6-bromo-3,4-dihydro-2H-chroman-2-carboxylic acid, followed by various electrophiles, in the search for new antibacterial and antifungal compounds with improved efficacy. 1H NMR, IR, and mass spectral data were used to determine the structures of these recently synthesized compounds. For their antibacterial and antifungal activities, all the produced com-pounds were tested. Besides their biological activities, these newly synthesized compounds were also docked into the active pocket of Dihydrofolate Reductase and Sterol 14-alpha demethylase to predict their binding modes concerning antibacterial and antifungal activities, respectively. More-over, these predictions would be utilized for the exploration of the mechanism of action on selected enzyme subunits.
objective:
Find out significant antimicrobial agents
Result:
Synthesis of 2-(6-bromochroman-2-yl)-1H-benzo[d]imidazole (4a-4y) derivatives was done using the classical Philipins condition. Spectral analysis revealed their structures. Amongst the synthesized scaffolds (4a-4y), target compounds 4r and 4w were active when compared with ciprofloxacin. Compound 4j was found to be highly active compared to clotrimazole. Ligands 4w and 4e exhibited better binding energy on Dihydro Folate Reductase and Sterol 14-alpha demethyl-ase (-7.1899 kcal/mol and -8.72613 kcal/mol) enzymes, respectively.
Conclusion:
The current investigation may have shown that the produced compounds differ from one another, regardless of their structure or observable biological activity. In the quest for a new group of antibacterial and antifungal molecules, these compounds may be useful to society.