Identification of Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS) inhibitors among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one
| Autor: | O. I. Gudzera, K. S. Boyarshin, Galyna P. Volynets, O. P. Kovalenko, Michail A. Tukalo, M. V. Protopopov, Sergiy M. Yarmoluk, Anna Yaremchuk, Volodymyr G. Bdzhola, Andriy G. Golub |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Modern medicine Tuberculosis medicine.drug_class Antibiotics 010402 general chemistry 01 natural sciences Microbiology Mycobacterium tuberculosis Inhibitory Concentration 50 Structure-Activity Relationship 03 medical and health sciences Antibiotic resistance Drug Discovery medicine Humans Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure biology Triazines Leucyl-tRNA synthetase Leucine—tRNA ligase General Medicine biology.organism_classification medicine.disease Anti-Bacterial Agents 0104 chemical sciences Molecular Docking Simulation 030104 developmental biology Enzyme Biochemistry chemistry Leucine-tRNA Ligase |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry. 31:201-207 |
| ISSN: | 1475-6374 1475-6366 |
| DOI: | 10.1080/14756366.2016.1190712 |
| Popis: | 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 IC50 of 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. |
| Databáze: | OpenAIRE |
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