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

Chiarelli Laurent R LR Mori Matteo M Beretta Giangiacomo G Gelain Arianna A Pini Elena E Sammartino Josè Camilla JC Stelitano Giovanni G Barlocco Daniela D Costantino Luca L Lapillo Margherita M Poli Giulio G Caligiuri Isabella I Rizzolio Flavio F Bellinzoni Marco M Tuccinardi Tiziano T Villa Stefania S Villa Stefania S Meneghetti Fiorella F

Journal of enzyme inhibition and medicinal chemistry 20191201 1

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]

PMID: 30889995

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Inhibitors of the salicylate synthase (MbtI) from Mycobacterium tuberculosis discovered by high-throughput screening.

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Stereocontrolled Synthesis of a Potential Transition-State Inhibitor of the Salicylate Synthase MbtI from Mycobacterium tuberculosis.

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Project description: Not available

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