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

Laurent R. Chiarelli; Matteo Mori; Giangiacomo Beretta; Arianna Gelain; Elena Pini; Josè Camilla Sammartino; Giovanni Stelitano; Daniela Barlocco; Luca Costantino; Margherita Lapillo; Giulio Poli; Isabella Caligiuri; Flavio Rizzolio; Marco Bellinzoni; Tiziano Tuccinardi; Stefania Villa; Fiorella Meneghetti

doi:10.1080/14756366.2019.1589462

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

Laurent R. Chiarelli, Matteo Mori, Giangiacomo Beretta, Arianna Gelain, Elena Pini, Josè Camilla Sammartino, Giovanni Stelitano, Daniela Barlocco, Luca Costantino, Margherita Lapillo, Giulio Poli, Isabella Caligiuri, Flavio Rizzolio, Marco Bellinzoni, Tiziano Tuccinardi, Stefania Villa, Fiorella Meneghetti

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	823-828
Number of pages	6
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	34
Issue number	1
DOIs	https://doi.org/10.1080/14756366.2019.1589462
Publication status	Published - Jan 1 2019

Keywords

antimycobacterial agent
drug design
molecular modelling
mycobactins
siderophores
Tuberculosis

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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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. (2019). New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents. Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 823-828. https://doi.org/10.1080/14756366.2019.1589462

Chiarelli, LR, Mori, M, Beretta, G, Gelain, A, Pini, E, Sammartino, JC, Stelitano, G, Barlocco, D, Costantino, L, Lapillo, M, Poli, G, Caligiuri, I , Rizzolio, F, Bellinzoni, M, Tuccinardi, T, Villa, S & Meneghetti, F 2019, 'New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents', Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 34, no. 1, pp. 823-828. https://doi.org/10.1080/14756366.2019.1589462

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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. ",

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AU - Gelain, Arianna

AU - Pini, Elena

AU - Sammartino, Josè Camilla

AU - Stelitano, Giovanni

AU - Barlocco, Daniela

AU - Costantino, Luca

AU - Lapillo, Margherita

AU - Poli, Giulio

AU - Caligiuri, Isabella

AU - Rizzolio, Flavio

AU - Bellinzoni, Marco

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AU - Meneghetti, Fiorella

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

Abstract

Keywords

ASJC Scopus subject areas

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