Improved synthesis of indazole-based sulfonamides for use in treating Mycobacterium tuberculosis

By Jillian Pabalan

Faculty Mentor: Davis Oldham

Abstract

Tuberculosis (TB) is a respiratory infection caused by Mycobacterium tuberculosis (MTB). Drug-resistant TB presents an ever-growing threat to global health, necessitating the development of new antitubercular drugs. MTB proliferation is facilitated in part by KasA, an enzyme critical to the formation of the bacterial cell wall; high-throughput screening has identified indazole-based sulfonamides as viable molecules to inhibit KasA function. Previously, only alkyl sulfonamides have been used for this purpose. We have synthesized a series of aryl sulfonamides employing a new synthetic route with the intention to improve yields from those present in the current literature basis. Accordingly, we propose a new synthetic route for the production of N-(1-alkyl-1H-indazol-6-yl)arylsulfonamides (where alkyl groups include methyl and ethyl substituents) through the alkylation and reduction of 6-nitroindazole, with subsequent sulfonamide formation. A total of 10 sulfonamides were synthesized and purified for use in viability assays.


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