Sulfonamides: a versatile scaffold for diverse biological activity
Samiksha J. Kokre, Rohini S. Kavalapure, Sushmitha S. Huddi, Shankar Gharge, Shankar G. Alegaon, Shriram D. Ranade, Meenaxi M. Maste, Ling Shing Wong, Ramith Ramu, D. Venu
Abstract
Sulfonamides remain a cornerstone of medicinal chemistry, serving as a versatile scaffold for the design of clinically significant therapeutics. While previous reviews have summarized their broad biological activities, this article uniquely integrates recent advances (2012–2024) in sulfonamide-based drug discovery with a focus on the rational design of potent and selective analogues. Beyond their classical antibacterial role, sulfonamide derivatives have shown emerging potential against cancer, diabetes, neurodegenerative and inflammatory disorders, and psychiatric diseases. This review emphasizes structure–activity relationship (SAR) insights, innovative scaffold engineering, bioisosteric modifications, and hybrid molecule design strategies that have reshaped the pharmacological landscape of sulfonamides. By synthesizing these developments, we provide a comprehensive, mechanism-informed perspective that bridges chemistry and biology, highlighting how contemporary synthetic strategies and molecular insights enable the creation of next-generation therapeutics. This integrative approach offers a clear roadmap for future research, underscoring the evolving relevance and therapeutic promise of sulfonamide scaffolds. • Sulfonamides act as flexible scaffolds in drug design, effectively mimicking protein structures. • . Sulfonamide derivatives show diverse bioactivities such as antidiabetic, anticancer, and anti-inflammatory effects. • Advances in sulfonamide synthesis have improved their availability for modern drug discovery. • This review highlights key developments of sulfonamides in medicinal chemistry from 2010-2024.