Design, synthesis, and molecular docking of cysteine-based sulphonamide derivatives as antimicrobial agents

BACKGROUND AND PURPOSE: The preponderance of microbial infections remains a global challenge. In the present study, synthesis of novel cysteine-based antimicrobial agents and their biological evaluation is reported. EXPERIMENTAL APPROACH: The reaction of p-toluenesulphonyl chloride with cysteine afforded 2-{[(4-methylphenyl)sulphonyl]amino}-3-sulphanylpropanoic acid (3) which was acetylated based on Lumiere-Barbier method using acetic anhydride. The ammonolysis of the acetylated compound (4) gave the carboxamide derivative (5) which reacted with aniline, aminopyridine and diaminopyrimidine via nickel catalyzed Buchwald-Hartwig amidation reaction to afford compounds 6a, 6b, and 6c, respectively. The compounds were characterized using FTIR, (1)H-NMR, (13)C-NMR, and elemental analysis. The in vitro antimicrobial activities were determined. Their physicochemical properties were generated in silico and the molecular docking studied bacterial and fungal infections. FINDINGS/RESULTS: Compounds 4, 6b, and 6c exhibited excellent in vitro antibacterial activities while compound 4 had the best antifungal activities. From the in silico antimicrobial results, compound 3 had a better binding affinity (-10.95 kcal/mol) than penicillin (-10.89 kcal/mol) while compounds 3 and 4 had binding affinities (-10.07 and -10.62kcal/mol) comparable to ketoconazole (-10.85 kcal/mol). CONCLUSION AND IMPLICATION: All the synthesized compounds exhibited significant antibacterial and antifungal activities and were confirmed to be potential antimicrobial agents.