Sulfonamides: Historical Perspectives, Therapeutic Insights, Applications, Challenges, and Synthetic Strategies

Sulfonamides, one of the earliest classes of synthetic antimicrobials, hold enduring significance in medicinal chemistry. This review highlights their evolution from antibiotics to multifunctional therapeutic agents, with applications in the treatment of diuretics, hypoglycemia, glaucoma, protease and kinase inhibition, and inflammatory diseases. It also outlines key synthetic strategies‐from traditional approaches to recent green and efficient methods. Environmental concerns and resistance‐related challenges are addressed, along with insights into novel delivery systems and future research opportunities. Overall, the review underscores the versatility and ongoing relevance of sulfonamides in modern drug discovery.