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A discovery of novel Mycobacterium tuberculosis pantothenate synthetase inhibitors based on the molecular mechanism of actinomycin D inhibition.

Abstract：

:Mycobacterium tuberculosis pantothenate synthetase is a potential anti-tuberculosis target, and a high-throughput screening system was previously developed to identify its inhibitors. Using a similar system, we screened a small library of compounds and identified actinomycin D (ActD) as a weak inhibitor of pantothenate synthetase. A new method was established to discover more effective inhibitors by determining the molecular mechanism of ActD inhibition followed by structure-based virtual screening. The molecular interaction of inhibition was determined by circular dichroism and tryptophan fluorescence quenching. The structure-based search and virtual screening were performed using the Molecular Operating Environment (MOE) program and SYBYL 7.5, respectively. Two inhibitors were identified with an IC(50) for pantothenate synthetase that was at least ten times better than that of ActD.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Yang Y,Gao P,Liu Y,Ji X,Gan M,Guan Y,Hao X,Li Z,Xiao C

doi

10.1016/j.bmcl.2011.05.021

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

3943-6

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00650-0

journal_volume

21

pub_type

杂志文章

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