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

ABSTRACT

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, ¹ H NMR, ¹³ C 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 IC ₅₀ 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.