Gudzera, Olga I., Golub, Andriy G., Bdzhola, Volodymyr G., Volynets, Galyna P., Kovalenko, Oksana P., Boyarshin, Konstantin S., Yaremchuk, Anna D., Protopopov, Mykola V., Yarmoluk, Sergiy M., and Tukalo, Michail A.
The increase of antibiotic resistance amongstMycobacterium tuberculosisstrains has become one of the most pressing problems of modern medicine. Therefore, the search of antibiotics againstM. tuberculosiswith novel mechanisms of action is very important. We have identified inhibitors ofM. tuberculosisleucyl-tRNA synthetase (LeuRS) among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one. The most active compounds 5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2H-[1,2,4]triazin-3-one and 5-(5-chloro-2-hydroxy-phenylamino)-2H-[1,2,4]triazin-3-one inhibitM. tuberculosisLeuRS with IC50of 7.6 μМ and 7.2 μМ, respectively. It was established that the inhibitory activity of compounds against pathogenic LeuRS is 10-fold better, than for human enzyme. [ABSTRACT FROM AUTHOR]