4‐Thiazolidinone/2,4‐Thiazolidinedione–Sulfonamide Hybrids: A Concise Review of Their Design and Pharmacological Significance

Molecular hybridization represents a promising strategy in drug‐design and the discovery of novel biologically active molecules, as it can enhance molecular affinity and potency while simultaneously reducing resistance and side effects. This review explores the recent advancements in the design, synthesis, and biological evaluation of hybrid molecules that combine sulfonamide with thiazolidinone or thiazolidine‐2,4‐dione scaffolds. The review covered studies published from 2009 to 2025 and focused exclusively on compounds containing both a sulfonamide moiety and a thiazolidinone or thiazolidinedione framework in the same molecule. These hybrid compounds have attracted considerable attention due to their potential to address the complexity of multifactorial diseases such as cancer, infections, and metabolic disorders, which often involve multiple biological pathways. By integrating features from both sulfonamides and thiazolidines, researchers have developed molecules with enhanced pharmacological profiles, including improved antimicrobial, anticancer, anti‐inflammatory, antidiabetic, and anticonvulsant activities. The review highlights how these hybrids often display multitarget effects, making them promising candidates for overcoming limitations of traditional single‐target drugs, such as resistance and limited efficacy. Key findings from recent studies are summarized, with a focus on the structural aspects that contribute to biological activity. Sulfonamide–thiazolidinone and sulfonamide–thiazolidinedione hybrids represent a versatile and valuable strategy in the search for new treatments for complex diseases.