Starting from the analysis of the hypothetical binding mode of our previous furan-based hit (I), we successfully achieved our objective to replace the nitro moiety, leading to the disclosure of a new lead exhibiting a strong activity against MbtI. Our best candidate 1 h displayed a K i of 8.8 µM and its antimycobacterial activity (MIC 99 = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. These results support the hypothesis that 5-phenylfuran-2-carboxylic derivatives are a promising class of MbtI inhibitors.

New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents

Lapillo M.;Poli G.;Tuccinardi T.;
2019-01-01

Abstract

Starting from the analysis of the hypothetical binding mode of our previous furan-based hit (I), we successfully achieved our objective to replace the nitro moiety, leading to the disclosure of a new lead exhibiting a strong activity against MbtI. Our best candidate 1 h displayed a K i of 8.8 µM and its antimycobacterial activity (MIC 99 = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. These results support the hypothesis that 5-phenylfuran-2-carboxylic derivatives are a promising class of MbtI inhibitors.
2019
Chiarelli, L. R.; Mori, M.; Beretta, G.; Gelain, A.; Pini, E.; Sammartino, J. C.; Stelitano, G.; Barlocco, D.; Costantino, L.; Lapillo, M.; Poli, G.; Caligiuri, I.; Rizzolio, F.; Bellinzoni, M.; Tuccinardi, T.; Villa, S.; Meneghetti, F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/997724
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