N-Acylsulfonamide: a valuable moiety to design new sulfa drug analogues

Sulfonamides are the oldest class of antibiotics, discovered more than 80 years ago. They are still used today despite the appearance of drug resistance phenomena that limit their prescription. Since the discovery and use of the first sulfa drugs, many analogues have been synthesized in order to obtain new active molecules able to circumvent bacterial resistance. Structurally similar to sulfonamide, the N-acylsulfonamide group arouses interest in the field of medicinal chemistry due to specific physico-chemical properties. We report here the synthesis and antibacterial/antibiofilm activities of 18 sulfa drug analogues with an N-acylsulfonamide moiety. These derivatives were obtained efficiently by sulfo-click reactions between readily available thioacid and sulfonyl azide synthons.

Automated summary

Sulfonamides are the oldest class of antibiotics, but their effectiveness has been limited by drug resistance. In this study, we synthesized 18 analogues of sulfa drugs with an N-acylsulfonamide moiety in order to overcome bacterial resistance. These derivatives were efficiently obtained through sulfo-click reactions using readily available thioacid and sulfonyl azide synthons.