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

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.

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, ¹H-NMR, ¹³C-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.

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).

All the synthesized compounds exhibited significant antibacterial and antifungal activities and were confirmed to be potential antimicrobial agents.