Synthesis, molecular docking and antimicrobial evaluation of novel benzoxazole derivatives

Abstract

In this research, previously and newly synthesized 5-amino-2-(4-substitutedphenyl/benzyl)benzoxazoles (3a–3l) and 2-substituted-5-(4-nitro/aminophenylsulfonamido)benzoxazoles (5a–5l, 6a–6l) were evaluated for their antimicrobial activities against Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212 and Mycobacterium tuberculosis H37RV ATCC 27294 and their drug-resistant isolates Candida albicans ATCC 10231 and Candida krusei ATCC 6258. The chemical structures of the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, LC–MS and elemental analysis. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at the minimum inhibitory concentration (MIC) values between 256 and 8 µg/mL. Compounds 3a, 3c and 3f exhibited significant antimycobacterial activity showing MIC value of 8 µg/mL against both M. tuberculosis and its drug-resistant isolate. InhA, the enoyl-acyl carrier protein reductase from M. tuberculosis, is one of the key enzymes in the FASII system involved in mycobacterial fatty acid elongation cycle, which has been validated as an effective antimicrobial target. Molecular docking into active site of InhA was performed on 3FNE.PDB file to understand ligand–protein interactions. The compounds obtained from this research can be used as scaffolds in the design of new potent drugs.