The present research focuses on the design, synthesis, and biological evaluation of novel thiazolidinone-based sulfonamide derivatives as dual antioxidant and anti-inflammatory agents. Sulfonamides are well-established pharmacophores exhibiting diverse therapeutic properties, while thiazolidinones possess pronounced radical scavenging and cyclooxygenase (COX) inhibitory potential. In this study, a hybridization approach was employed to combine these two bioactive scaffolds into a single molecular framework with the aim of achieving synergistic pharmacological effects. The compounds were synthesized through a multistep procedure involving Schiff base formation, cyclization with thioglycolic acid, and condensation with substituted aromatic aldehydes. The synthesized derivatives were structurally confirmed through FTIR, ¹H NMR, and CHNS elemental analysis, which verified the presence of characteristic functional groups and the successful formation of the thiazolidinone ring. The in-vitro antioxidant activity of the compounds was evaluated using DPPH, ABTS, and FRAP assays, with ascorbic acid as the reference standard. The derivatives bearing electron-donating substituents such as –OH and –OCH₃ exhibited the highest free radical scavenging potential (IC₅₀ = 36.8–39.4 µg/mL), while those with electron-withdrawing groups (–Cl, –NO₂) showed comparatively lower activity, indicating that resonance stabilization plays a key role in enhancing antioxidant behavior. The anti-inflammatory potential was assessed through protein denaturation and HRBC membrane stabilization assays using diclofenac sodium as a reference, where similar trends were observed compounds with electron-donating substituents demonstrated superior membrane-stabilizing and protein-protective effects. Statistical analysis using one-way ANOVA followed by Tukey's post-hoc test confirmed the significance of the observed biological activities (p < 0.05). Overall, the study establishes a clear structure–activity relationship (SAR) correlating electronic effects of substituents with pharmacological performance. These findings highlight the potential of thiazolidinone-based sulfonamide hybrids as promising leads for the development of multifunctional therapeutic agents targeting oxidative stress and inflammatory disorders.
Keywords: Thiazolidinone, Sulfonamide, Antioxidant, Anti-inflammatory, Schiff base, Molecular hybridization, FTIR, ¹H NMR, In-vitro assays.
How to cite this article: Thakare V, Chakkarapani SK, Karandikar P, Sompura K, Patel SD, Nath S, Vishwakarma DK, Patil SS, Synthesis and SAR Exploration of Novel Thiazolidinone Sulfonamide Molecular Hybrids for Synergistic Mitigation of Oxidative Stress and Inflammatory Signaling. Int J Drug Deliv Technol. 2026;16(4s): 840-847; DOI: 10.25258/ijddt.16.4s.97
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Conflict of interest: None