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

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 an...

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Autores principales: Chiarelli, Laurent R., Mori, Matteo, Beretta, Giangiacomo, Gelain, Arianna, Pini, Elena, Sammartino, Josè Camilla, Stelitano, Giovanni, Barlocco, Daniela, Costantino, Luca, Lapillo, Margherita, Poli, Giulio, Caligiuri, Isabella, Rizzolio, Flavio, Bellinzoni, Marco, Tuccinardi, Tiziano, Villa, Stefania, Meneghetti, Fiorella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Short Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427685/
https://www.ncbi.nlm.nih.gov/pubmed/30889995
http://dx.doi.org/10.1080/14756366.2019.1589462
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author Chiarelli, Laurent R.
Mori, Matteo
Beretta, Giangiacomo
Gelain, Arianna
Pini, Elena
Sammartino, Josè Camilla
Stelitano, Giovanni
Barlocco, Daniela
Costantino, Luca
Lapillo, Margherita
Poli, Giulio
Caligiuri, Isabella
Rizzolio, Flavio
Bellinzoni, Marco
Tuccinardi, Tiziano
Villa, Stefania
Meneghetti, Fiorella
author_facet Chiarelli, Laurent R.
Mori, Matteo
Beretta, Giangiacomo
Gelain, Arianna
Pini, Elena
Sammartino, Josè Camilla
Stelitano, Giovanni
Barlocco, Daniela
Costantino, Luca
Lapillo, Margherita
Poli, Giulio
Caligiuri, Isabella
Rizzolio, Flavio
Bellinzoni, Marco
Tuccinardi, Tiziano
Villa, Stefania
Meneghetti, Fiorella
author_sort Chiarelli, Laurent R.
collection PubMed
description 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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spelling pubmed-64276852019-03-25 New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents Chiarelli, Laurent R. Mori, Matteo Beretta, Giangiacomo Gelain, Arianna Pini, Elena Sammartino, Josè Camilla Stelitano, Giovanni Barlocco, Daniela Costantino, Luca Lapillo, Margherita Poli, Giulio Caligiuri, Isabella Rizzolio, Flavio Bellinzoni, Marco Tuccinardi, Tiziano Villa, Stefania Meneghetti, Fiorella J Enzyme Inhib Med Chem Short Communication 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. Taylor & Francis 2019-03-20 /pmc/articles/PMC6427685/ /pubmed/30889995 http://dx.doi.org/10.1080/14756366.2019.1589462 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Chiarelli, Laurent R.
Mori, Matteo
Beretta, Giangiacomo
Gelain, Arianna
Pini, Elena
Sammartino, Josè Camilla
Stelitano, Giovanni
Barlocco, Daniela
Costantino, Luca
Lapillo, Margherita
Poli, Giulio
Caligiuri, Isabella
Rizzolio, Flavio
Bellinzoni, Marco
Tuccinardi, Tiziano
Villa, Stefania
Meneghetti, Fiorella
New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents
title New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents
title_full New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents
title_fullStr New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents
title_full_unstemmed New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents
title_short New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents
title_sort new insight into structure-activity of furan-based salicylate synthase (mbti) inhibitors as potential antitubercular agents
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427685/
https://www.ncbi.nlm.nih.gov/pubmed/30889995
http://dx.doi.org/10.1080/14756366.2019.1589462
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