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

Authors :
Chiarelli, Laurent
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
University of Pavia
Università degli Studi di Milano [Milano] (UNIMI)
University of Modena and Reggio Emilia
Partenaires INRAE
University of Pisa - Università di Pisa
National Cancer Institute of Aviano
University of Ca’ Foscari [Venice, Italy]
Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5))
Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
This work was funded by University of Milan (Linea B), and the Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Programme (2018–2022) - Dept. of Biology and Biotechnology 'L. Spallanzani', University of Pavia.
Università degli Studi di Pavia = University of Pavia (UNIPV)
Università degli Studi di Milano = University of Milan (UNIMI)
Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Source :
Journal of Enzyme Inhibition and Medicinal Chemistry, Journal of Enzyme Inhibition and Medicinal Chemistry, Informa Healthcare, 2019, 34 (1), pp.823-828. ⟨10.1080/14756366.2019.1589462⟩, Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, 34 (1), pp.823-828. ⟨10.1080/14756366.2019.1589462⟩, Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 34, Iss 1, Pp 823-828 (2019)
Publication Year :
2019

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.<br />GRAPHICAL ABSTRACT

Details

ISSN :
14756374 and 14756366
Volume :
34
Issue :
1
Database :
OpenAIRE
Journal :
Journal of enzyme inhibition and medicinal chemistry
Accession number :
edsair.pmid.dedup....819ebdb9e7fca741cbabce2b348c7a91
Full Text :
https://doi.org/10.1080/14756366.2019.1589462⟩