Anti-mycobacterial activity of a bis-sulfonamide
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Since the introduction of prontosil over 70 years ago, sulfa drugs have been widely used to treat a broad spectrum of infectious microorganisms. The bioactive component of prontosil, sulfanilamide (1), inhibits 6-hydroxymethyl-7,8-dihydropteroate synthase (DHPS) selectively limiting folate synthesis in prokaryotes and lower eukaryotes thus disrupting the integrity of their DNA synthesis.1 The evolution of drug resistance in infectious microorganisms underpins an immense and ongoing need for new therapies to treat infectious diseases. The identification of new and novel chemical entities with activity against cells infected with the microorganism is a crucial component of this anti-infective drug development pathway.2 Although sulfonamides are not specifically incorporated into current tuberculosis treatment, many sulfur-3,4, sulfonyl-4,5,6, and sulfonamide-containing7,8 compounds are active against mycobacteria. This prompted us to screen our growing library of triazole-based sulfonamides (e.g.-2) for antimycobacterial activity. Herein we report identification of a novel bis-sulfonamide with antimicrobial activity against Mycobacterium smegmatis that is relatively inert toward common bacterial and fungal strains.
Bioorganic & Medicinal Chemistry Letters