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 journalArticle

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 languageEnglish
Pages (from-to)823-828
Number of pages6
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume34
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • antimycobacterial agent
  • drug design
  • molecular modelling
  • mycobactins
  • siderophores
  • Tuberculosis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents'. Together they form a unique fingerprint.

  • Cite this

    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