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Identification of Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS) inhibitors among the derivatives of 5-phenylamino-2H-[1,2,4]triazin-3-one.
- Source :
-
Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2016; Vol. 31 (sup2), pp. 201-207. Date of Electronic Publication: 2016 May 31. - Publication Year :
- 2016
-
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 IC <subscript>50</subscript> 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.
- Subjects :
- Anti-Bacterial Agents analysis
Anti-Bacterial Agents isolation & purification
Dose-Response Relationship, Drug
Humans
Inhibitory Concentration 50
Leucine-tRNA Ligase metabolism
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Triazines chemical synthesis
Triazines chemistry
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Leucine-tRNA Ligase antagonists & inhibitors
Mycobacterium tuberculosis drug effects
Mycobacterium tuberculosis enzymology
Triazines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1475-6374
- Volume :
- 31
- Issue :
- sup2
- Database :
- MEDLINE
- Journal :
- Journal of enzyme inhibition and medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27241561
- Full Text :
- https://doi.org/10.1080/14756366.2016.1190712