Screening of novel inhibitors of indole3glycerol phosphate synthase from Mycobacterium tuberculosis
ZHOU Tao1,2, WANG Fei-Fei3, HUANG Qiang4, WANG Hong-Hai4, SHEN Hong-Bo2
1. School of Life Sciences, Shanghai University, Shanghai 200444, China; 2. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; 3. Department of Medical Microbiology and Parasitology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 4. School of Life Sciences, Fudan University, Shanghai 200433, China
Abstract：In this study, the structure of indole-3-glycerol phosphate synthase (IGPS) from Mycobacterium tuberculosis (M. tuberculosis) H37Rv was obtained by homologous modeling. Based on the IGPS structure, virtual screening was carried out to select novel inhibitors from the Maybridge database with about sixty thousands organic compounds. Through biological selection, one compound, named ATB26, was identified as a potential inhibitor of IGPS, which showed potent antimycobacterial activity not only against M. tuberculosis H37Rv, but also against clinical isolates of multidrug-resistant M. tuberculosis strains with (minimal inhibition concentration, MIC) of 0.1 μg/ml. ATB26 could bound tightly to IGPS in vitro and obviously inhibited activity of IGPS. These results suggest that ATB26 is a novel potent inhibit of IGPS, and that IGPS might be a potential target for the development of new anti-tuberculosis drugs.
