Yanhong Niu , Zhili Wu , Qianfang Hu , Yuchen Wu , Qihua Jiang , Xiaolan Yang
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引用次数: 0
Abstract
Acetohydroxy acid synthase (AHAS) is a key enzyme that catalyzes the synthesis of branched-chain amino acids, which is indispensable for the survival and growth of Mycobacterium tuberculosis (Mtb). Aim to discover new AHAS inhibitors from natural products, here we performed computer assistant target-based screening for Mtb-AHAS inhibitors using Discovery Studio on TCMSP and SELLECK libraries. Mtb-AHAS structure was first simulated and verified for docking, and 80 compounds with top LIBDOCK and CDDOCK scores were obtained. By experimental verification, four compounds namely Salvianolic acid A, Embelin, Celastrol and Wushanicaritin showed inhibition potency against Mtb-AHAS with IC50 ranging from 805.5 nM–32.36 μM. The most potential inhibitor Celastrol exhibited bacteriostatic activity for both Mycobacterium smegmatis and Mycobacterium tuberculosis with MIC of 62.5 μM and 80 μM, respectively. This study revealed that Celastrol is the potential Mtb-AHAS inhibitor as an anti-tuberculosis lead compound.
期刊介绍：
Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides.
The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.
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