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Information × Registration Number 0219U000114, 0117U003547 , R & D reports Title Multitarget drug discovery to overcome antibiotic resistance in Mycobacterium tuberculosis popup.stage_title Head Tukalo Mykhailo, Доктор біологічних наук Registration Date 15-01-2019 Organization Institute of Molecular Biology and Genetics of NASU popup.description2 We have built homology models and investigated structural characteristics of leucyl-tRNA synthetase (LeuRS) and methionyl-tRNA synthetase (MetRS) M. tuberculosis.We performed virtual screening of compound collection containing about 250,000 compounds using molecular docking and pharmacophore modeling and selected about 1000 compounds for investigation of their inhibitory activity toward recombinant LeuRS and MetRS M. tuberculosis. Recombinant proteins LeuRS and MetRS M. tuberculosis were expressed and purified in soluble form. Accordingly to the results of in vitro testing, we have identified 15 compounds with dual-targeted inhibitory activity toward LeuRS and MetRS M. tuberculosis.We have identified inhibitor 4-{[4-(4-Bromo-phenyl)-thiazol-2-yl]hydrazonomethyl}-2-methoxy-6-nitro-phenol which simultaneously inhibits LeuRS and MetRS with ІС50 values of 11.2 and 12.1 µМ and possesses antibacterial activity toward pathogenic strain M. tuberculosis H37Rv with MIC value of 25 µМ. Product Description popup.authors . Волинець Галина Петрівна Бджола Володимир Григорович Гудзера Ольга Йосипівна Коваленко Оксана Петрівна Крикливий Іван Андрійович Рибак Марія Юріївна Старосила Сергій Анатолійович Яремчук Ганаа Дмитрівна Ярмолюк Сергій Миколайович popup.nrat_date 2020-04-02 Close