Green Synthesis of Sulfonamide Derivatives Using Natural Catalysts: Evaluation of Antimicrobial and Anticancer Activities

Sulfonamide derivatives represent a crucial scaffold in medicinal chemistry, yet their conventional synthesis often necessitates environmentally adverse conditions. This study introduces a green synthetic protocol for novel sulfonamide derivatives, generated via reacting aromatic amines with benzenesulfonyl and ۴‑methylbenzenesulfonyl chlorides under both conventional (NaOH) and green catalytic conditions. The key innovation lies in utilizing aqueous extracts of natural orange and banana peels as highly efficient, non-toxic, and cost-effective catalysts, achieving synthetic yields exceeding ۹۰% for several products. Biological evaluation demonstrated significant antibacterial activity, exemplified by N‑(۴‑chlorophenyl)۴‑methylbenzenesulfonamide (MIC ۲۵ µM against Staphylococcus aureus), and anticancer activity, with N‑(۴‑ethylphenyl)  ۴‑methylbenzenesulfonamide showing IC₅₀ values around ۲۵ µM against HT‑۲۹ colon cancer cells. The biological evaluation confirmed that structural features strongly influence activity: dichloro‑substituted derivatives exhibited the highest anticancer potency, with cytotoxicity values approaching those of the standard reference drug, while ortho‑tolyl and para‑chlorophenyl derivatives showed the strongest antibacterial inhibition zones comparable to the reference sulfonamide. These results highlight the dual bioactivity of the synthesized compounds and the novelty of employing natural catalysts in sustainable pharmaceutical synthesis. Overall, the findings emphasize the importance of rational structural design in optimizing these biologically active sulfonamides, establishing this biomass-derived catalytic route as an environmentally friendly pathway for developing promising lead structures for both antibacterial and anticancer drug development.

کلیدواژه ها:

Sulfonamide derivatives ، Green synthesis ، Antimicrobial activity ، Anticancer evaluation ، MTT assay