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© Institut Pasteur
Cells infected for 24 hrs with C. Trachomatis. The cell nuclei are labelled in blue, the bacteria appear yellow, within the inclusion lumen. A bacterial protein secreted out the inclusion into the host cytoplasm id labelled in red.
Publication : Journal of enzyme inhibition and medicinal chemistry

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

Team: Structural biology of metabolic enzymes and complexes
Team: Structural Microbiology
Member: Marco Bellinzoni
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of enzyme inhibition and medicinal chemistry - 01 Dec 2019

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,

Link to Pubmed [PMID] – 30889995

Link to DOI – 10.1080/14756366.2019.1589462

J Enzyme Inhib Med Chem 2019 Dec; 34(1): 823-828

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.