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

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 Ki of 8.8?µM and its antimycobacterial activity (MIC99?=?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.

SUBMITTER: Chiarelli LR 

PROVIDER: S-EPMC6427685 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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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<sub>i</sub> of 8.8 µM and its antimycobacterial activity (MIC<sup>99</sup> = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. These results support the hypothesis that 5-phenylfuran-2-carboxylic  ...[more]

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