Exploring the role of the heterocyclic moiety of 5-(4-nitrophenyl)-2-furoic acid, a promising inhibitor of MBTI from mycobacterium tuberculosis

Tuberculosis nowadays ranks as the first leading cause of death from an infectious disease worldwide,1 especially because of the appearance of multi-drug resistant forms. Efficient iron acquisition is crucial for the pathogenesis of Mycobacterium tuberculosis (Mtb), since it serves as a cofactor in many essential biological processes. Given the high toxicity of free iron, Mtb synthesizes siderophores to assimilate it. The bifunctional salicylate synthase MbtI catalyzes the first step of mycobactin biosynthesis through the conversion of the primary metabolite chorismate to salicylic acid via isochorismate.2,3 By means of a receptor-based virtual screening approach, we identified MM40 a new furan derivative targeting this salicylate synthase (MbtI). Herein, we report on a structure activity relationship study on MM40 to investigate the role of the heterocyclic moiety for the interaction with the enzyme.