RRC ID 50864
Author Taira J, Ito T, Nakatani H, Umei T, Baba H, Kawashima S, Maruoka T, Komatsu H, Sakamoto H, Aoki S.
Title In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening.
Journal Int J Mycobacteriol
Abstract BACKGROUND:Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB) agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids.
MATERIALS AND METHODS:We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS). Following the selection of such compounds, their antimycobacterial activity was examined.
RESULTS:With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug.
CONCLUSION:The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.
Volume 6(2)
Pages 142-148
Published 2017-1-1
DOI 10.4103/ijmy.ijmy_24_17
PII IntJMycobacteriol_2017_6_2_142_206597
PMID 28559515
MeSH Antitubercular Agents / chemistry* Antitubercular Agents / pharmacology* Computer Simulation Drug Design Drug Evaluation, Preclinical / methods* Humans Mycobacterium tuberculosis / drug effects* Mycobacterium tuberculosis / enzymology Mycobacterium tuberculosis / genetics Mycobacterium tuberculosis / metabolism Mycolic Acids / metabolism Tuberculosis / microbiology
Times Cited 5
General Microbes JCM 20379