Design and Synthesis of Novel Sulfonamide-Derived Triazoles and Bioactivity Exploration.

Objective: Due to the incidence of resistance, a series of sulfonamide-derived 1,2,4- triazoles were synthesized and evaluated.

Method: The novel sulfonamide-derived 1,2,4-triazoles were prepared starting from commercial acetaniline and chlorosulfonic acid by sulfonylation, aminolysis, N-alkylation and so on. The antimicrobial activity of the synthesized compounds were evaluated in vitro by two-fold serial dilution technique.

Results: In vitro antimicrobial evaluation found that 2-chlorobenzyl sulfonamide 1,2,4-triazole 7c exhibited excellent antibacterial activities against MRSA, B. subtilis, B. typhi and E. coli with MIC values of 0.02-0.16 μmol/mL, which were comparable or even better than Chloromycin. The preliminary mechanism suggested that compound 7c could effectively bind with DNA, and also it could bind with human microsomal heme through hydrogen bonds in molecular docking. Computational chemical studies were performed on compound 7c to understand the structural features that are essential for activity. Additionally, compound 7c could generate a small amount of reactive oxygen species (ROS).

Conclusion: Compound 7c could serve as a potential clinical antimicrobial candidate.