1,3,4-Oxadiazole-sulfonamide hybrids: recent advances in biological activities, structure-activity relationships, and therapeutic applications.

Molecular hybridization has emerged as an effective strategy in medicinal chemistry for the development of multifunctional therapeutic agents with improved biological performance. Among the various hybrid scaffolds investigated, 1,3,4-oxadiazole-sulfonamide hybrids have gained considerable attention owing to the complementary pharmacological properties of both pharmacophores. The integration of the 1,3,4-oxadiazole nucleus and sulfonamide moiety within a single molecular framework has generated structurally diverse compounds exhibiting promising activities against a broad range of biological targets. This review provides a comprehensive overview of the biological activities and structure-activity relationships (SARs) of 1,3,4-oxadiazole-sulfonamide hybrids reported over the past two decades. Particular emphasis is placed on their antimicrobial, anticancer, anti-Alzheimer, anti-HIV, antidiabetic, anti-inflammatory, antioxidant, antimalarial, anti-glaucoma, and carbonic anhydrase inhibitory activities. Furthermore, the influence of key structural modifications on biological performance is critically discussed, highlighting the pharmacophoric features and substitution patterns associated with enhanced potency and selectivity. Collectively, the available evidence demonstrates the remarkable therapeutic versatility of 1,3,4-oxadiazole-sulfonamide hybrids and supports their continued exploration as promising scaffolds for future drug discovery and development.