Synthesis, Characterization, Antioxidant Evaluation, Cytotoxicity Studies, and Molecular Docking of Novel Sulfonamide...

A series of novel sulfonamide derivatives (4a-i) was synthesized via a three-step sequence involving Schiff base formation, sodium borohydride reduction to the corresponding secondary amines (2a-i), and subsequent treatment with p-toluenesulfonyl chloride in the presence of sodium carbonate. The structures of all intermediates and final products were unambiguously confirmed by FT-IR, ¹H NMR, ¹³C NMR, and HRMS analyses. The antioxidant activity of the target compounds was assessed using the DPPH radical scavenging assay with BHT as a reference standard. Among the synthesized derivatives, compound 4d exhibited the most pronounced antioxidant activity, surpassing BHT at concentrations of 37.5 and 62.5 µg/mL. The cytotoxicity of the compounds was evaluated against human ovarian carcinoma (A2780) and prostate cancer (LNCaP) cell lines using the MTT assay, with docetaxel as a positive control. Compounds 4g, 4h, and 4i demonstrated the highest cytotoxic potency against both cell lines, with compound 4h displaying a log IC₅₀ value of 1.343 µg/mL against LNCaP cells. Structure-activity relationship analysis suggests that the methoxy substituent enhances cytotoxic activity, likely through increased lipophilicity and electron-donating effects facilitating interactions with biological targets. Molecular docking studies were performed to further rationalize the observed biological activities.