Afficher la couverture 'New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents | Chiarelli, Laurent' en grand format
/5

0 avis

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

Archive ouverte

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

Edité par CCSD ; Informa Healthcare -

International audience. 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.

Suggestions

Du même auteur

Shedding X-ray Light on the Role of Magnesium in the Activity of Mycobacterium tuberculosis Salicylate Synthase (MbtI) for Drug Design

Archive ouverte | Mori, Matteo | CCSD

International audience. The Mg2+-dependent Mycobacterium tuberculosis salicylate synthase (MbtI) is a key enzyme involved in the biosynthesis of siderophores. Because iron is essential for the survival and pathogeni...

Structural Study of a New MbtI-Inhibitor Complex: Towards an Optimized Model for Structure-Based Drug Discovery

Archive ouverte | Mori, Matteo | CCSD

International audience. MbtI from Mycobacterium tuberculosis (Mtb) is a Mg2+-dependent salicylate synthase, belonging to the chorismate-utilizing enzyme (CUE) family. As a fundamental player in iron acquisition, Mbt...

Thiophenecarboxamide Derivatives Activated by EthA Kill Mycobacterium tuberculosis by Inhibiting the CTP Synthetase PyrG

Archive ouverte | Mori, Giorgia | CCSD

International audience. To combat the emergence of drug-resistant strains of Mycobacterium tuberculosis, new antitubercular agents and novel drug targets are needed. Phenotypic screening of a library of 594 hit comp...

Chargement des enrichissements...