First triclosan-based macrocyclic inhibitors of InhA enzyme.

First triclosan-based macrocyclic inhibitors of InhA enzyme.
Bioorg Chem. 2019 Dec 06;95:103498
Authors: Rodriguez F, Saffon N, Sammartino JC, Degiacomi G, Pasca MR, Lherbet C
Abstract
Two macrocyclic derivatives based on the triclosan frame were designed and synthesized as inhibitors of Mycobacterium tuberculosis InhA enzyme. One of the two molecules M02 displayed promising inhibitory activity against InhA enzyme with an IC50 of 4.7 μM. Molecular docking studies of these two compounds were performed and confirmed that M02 was more efficient as inhibitor of InhA activity. These molecules are the first macrocyclic direct inhibitors of InhA enzyme able to bind into the substrate pocket. Furthermore, these biaryl ether compounds exhibited antitubercular activities comparable to that of triclosan against M. tuberculosis H37Rv strain.
PMID: 31855823 [PubMed - as supplied by publisher]

Source: Bioorganic Chemistry - December 5, 2019 Category: Chemistry Authors: Rodriguez F, Saffon N, Sammartino JC, Degiacomi G, Pasca MR, Lherbet C Tags: Bioorg Chem Source Type: research