Synthesis, Molecular Docking, and DFT Studies of Some New 2,5-Disubstituted Benzoxazoles as Potential Antimicrobial and Cytotoxic Agents

Abstract

In this study, a total of 17 piece 2,5-disubstituted benzoxazole derivatives were synthesized, 2 of which were not original, their antimicrobial activities were determined using microdilution method and their in vitro cytotoxic activities were investigated on MCF-7 and A549 cells by MTT test. When the activity results are examined, although the antibacterial effects of benzoxazole derivatives are weaker than standard drugs; 3N13 and 3N19 against Candida albicans isolate showed the closest activity to fluconazole with MIC: 16 µg/ml. The cytotoxicity test was measured at a concentration of 100 µM and a 24-h incubation period. The results showed that the compounds had weak activities against two cell lines. Molecular docking studies of synthesized compounds were performed on sterol 14α-demethylase protein (CYP51) and protein-ligand interactions of 3N13, the most effective derivative against C. albicans isolate, were showed (PDB: 5TZ1). Estimated ADME profiles of compounds were calculated and also 3N13’s were calculated HUMO-LUMO energies, molecular electrostatic potential analysis, and geometric optimization parameters with 6-311 G+ (d,p) base set using DFT/B3LYP theory, and the results were displayed.

Keywords:

• ADME prediction
• antimicrobial activity
• benzoxazole
• cytotoxicity
• molecular docking

Acknowledgment

NMR analysis of the compounds were performed by Erciyes University Technology and Research Center (TAUM) and HRMS analysis were performed by Bilkent University National Nanotechnology Research Center (UNAM).

Disclosure statement

No potential conflict of interest was reported by the authors.