title: Identification of Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS) inhibitors among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one.
abstract: The increase of antibiotic resistance amongst Mycobacterium tuberculosis strains has become one of the most pressing problems of modern medicine. Therefore, the search of antibiotics against M. tuberculosis with novel mechanisms of action is very important. We have identified inhibitors of M. tuberculosis leucyl-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 inhibit M. tuberculosis LeuRS 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.
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Olga I
authors.initials: OI
authors.lastname: Gudzera
authors.affiliation: b OTAVA Ltd. , Vaughan , ON , Canada.
authors.forename: Andriy G
authors.initials: AG
authors.lastname: Golub
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Volodymyr G
authors.initials: VG
authors.lastname: Bdzhola
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Galyna P
authors.initials: GP
authors.lastname: Volynets
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Oksana P
authors.initials: OP
authors.lastname: Kovalenko
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Konstantin S
authors.initials: KS
authors.lastname: Boyarshin
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Anna D
authors.initials: AD
authors.lastname: Yaremchuk
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Mykola V
authors.initials: MV
authors.lastname: Protopopov
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Yarmoluk
authors.affiliation: a Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine and.
authors.forename: Michail A
authors.initials: MA
authors.lastname: Tukalo
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D007935:Leucine-tRNA Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000614130:5-phenylamino-2H-(1,2,4)triazin-3-one; D000900:Anti-Bacterial Agents; D014227:Triazines; D007935:Leucine-tRNA Ligase
keywords: Aminoacylation assay; Mycobacterium tuberculosis; inhibitor; leucyl-tRNA synthetase; virtual screening