Newly synthesized sulfonamide derivatives explored for DNA binding, enzyme inhibitory, and cytotoxicity activities: a...

The current research work reports the synthesis of three 4-((3-arylthiazolo[3,4-d]isoxazol-5-yl)amino)benzene sulfonamide derivatives with a thaizaole(3,4-d)isoxazole-based fused ring heterocyclic system. The synthesized and characterized derivatives, namely, 4-(3-(2-hydroxy-3-methoxyphenyl)thiazolo[3,4-d]soxazole-5-ylamino)benzenesulfonamide (YM-1), 4-(3-(4-chlorophenyl)isoxazolo[3,4-d]thiazol-5-ylamino)benzenesulfonamide (YM-2), and 4-(3-(3-hydroxyphenyl)isoxazolo[3,4-d]thiazol-5-ylamino)benzenesulfonamide (YM-3) were further explored for their binding interactions with DNA and enzymes (urease and carbonic anhydrase). Cytotoxicity of these derivatives for both healthy (HEK-293) and cancerous (MG-U87) cells was determined by MTT analysis. Both experimental (UV-visible, fluorescence, cyclic voltammetry, and viscometry) and theoretical (molecular docking) profiles suggested that these derivatives are good DNA binders. All the derivatives interacted with DNA via mixed intercalative and groove binding interactions. However, the evaluated DNA binding parameters (K _b, ΔG, and n) were comparatively greater for YM-1. Docking data (K _b and ΔG) for binding of these derivatives with enzymes also supported that YM-1 was a comparatively better inhibitor for carbonic anhydrase. However, experimentally evaluated IC₅₀ (1.90 ± 0.02 μM) and % inhibition (57.93%) were found to be greater for YM-2 against urease enzyme. All the derivatives show dose-dependent cytotoxicity (70-90%) against MG-U87 cancer cells. Conversely, only one concentration of YM-1 (120 μM) showed less toxicity (50.28% with IC₅₀ of 1.154 ± 0.317 μM) than that of the positive control (52.22%) for healthy cells. Overall findings suggested sulfonamide derivative YM-1 is a better candidate for DNA binding, enzyme inhibition as well as anticancer activity.