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Your search keyword '"Golub, Andriy G."' showing total 3 results
Start Over Author "Golub, Andriy G." Publisher elsevier science
3 results on '"Golub, Andriy G."'

1. Discovery of potent anti-tuberculosis agents targeting leucyl-tRNA synthetase.

Author

Gudzera OI, Golub AG, Bdzhola VG, Volynets GP, Lukashov SS, Kovalenko OP, Kriklivyi IA, Yaremchuk AD, Starosyla SA, Yarmoluk SM, and Tukalo MA

Subjects
Amino Acid Sequence, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Humans, Leucine-tRNA Ligase chemistry, Leucine-tRNA Ligase metabolism, Models, Molecular, Molecular Sequence Data, Mycobacterium tuberculosis chemistry, Nitrophenols chemical synthesis, Nitrophenols chemistry, Nitrophenols pharmacology, Protein Structure, Tertiary, Sequence Alignment, Tuberculosis microbiology, Antitubercular Agents chemistry, Antitubercular Agents pharmacology, Leucine-tRNA Ligase antagonists & inhibitors, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis enzymology, Tuberculosis drug therapy
Abstract

Tuberculosis is a serious infectious disease caused by human pathogen bacteria Mycobacterium tuberculosis. Bacterial drug resistance is a very significant medical problem nowadays and development of novel antibiotics with different mechanisms of action is an important goal of modern medical science. Leucyl-tRNA synthetase (LeuRS) has been recently clinically validated as antimicrobial target. Here we report the discovery of small-molecule inhibitors of M. tuberculosis LeuRS. Using receptor-based virtual screening we have identified six inhibitors of M. tuberculosis LeuRS from two different chemical classes. The most active compound 4-{[4-(4-Bromo-phenyl)-thiazol-2-yl]hydrazonomethyl}-2-methoxy-6-nitro-phenol (1) inhibits LeuRS with IC50 of 6μM. A series of derivatives has been synthesized and evaluated in vitro toward M. tuberculosis LeuRS. It was revealed that the most active compound 2,6-Dibromo-4-{[4-(4-nitro-phenyl)-thiazol-2-yl]-hydrazonomethyl}-phenol inhibits LeuRS with IC50 of 2.27μM. All active compounds were tested for antimicrobial effect against M. tuberculosis H37Rv. The compound 1 seems to have the best cell permeability and inhibits growth of pathogenic bacteria with IC50=10.01μM and IC90=13.53μM., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
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2. Identification of apoptosis signal-regulating kinase 1 (ASK1) inhibitors among the derivatives of benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one.

Author

Starosyla SA, Volynets GP, Lukashov SS, Gorbatiuk OB, Golub AG, Bdzhola VG, and Yarmoluk SM

Subjects
Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Binding Sites, Enzyme Assays, High-Throughput Screening Assays, Humans, Hypoglycemic Agents chemical synthesis, Hypoglycemic Agents chemistry, Immunologic Factors chemical synthesis, Immunologic Factors chemistry, MAP Kinase Kinase Kinase 5 chemistry, Neuroprotective Agents chemical synthesis, Neuroprotective Agents chemistry, Protein Binding, Protein Kinase Inhibitors chemical synthesis, Pyrroles chemical synthesis, Recombinant Proteins, Small Molecule Libraries chemical synthesis, Structure-Activity Relationship, Thiazoles chemical synthesis, User-Computer Interface, MAP Kinase Kinase Kinase 5 antagonists & inhibitors, Protein Kinase Inhibitors chemistry, Pyrroles chemistry, Small Molecule Libraries chemistry, Thiazoles chemistry
Abstract

Apoptosis signal-regulating kinase 1 (ASK1) plays important roles in the pathogenesis of type 1 and type 2 diabetes, autoimmune disorders, cancer and neurodegenerative diseases suggesting that small compounds inhibiting ASK1 could be used for the treatment of these pathologies. We have identified novel chemical class of ASK1 inhibitors, namely benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one, using molecular modeling techniques. It was found that the most active compound 1-(6-fluoro-benzothiazol-2-yl)-3-hydroxy-5-[3-(3-methyl-butoxy)-phenyl]-4-(2-methyl-2,3-dihydro-benzofuran-5-carbonyl)-1,5-dihydro-pyrrol-2-one (BPyO-34) inhibits ASK1 with IC50 of 0.52μM in vitro in kinase assay. The structure-activity relationships of 34 derivatives of benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one have been studied and binding mode of this chemical class has been proposed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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3. Discovery and characterization of synthetic 4'-hydroxyflavones-New CK2 inhibitors from flavone family.

Author

Golub AG, Bdzhola VG, Ostrynska OV, Kyshenia IV, Sapelkin VM, Prykhod'ko AO, Kukharenko OP, and Yarmoluk SM

Subjects
Binding Sites, Casein Kinase II genetics, Casein Kinase II metabolism, Drug Design, Drug Evaluation, Preclinical, Flavones chemical synthesis, Flavones metabolism, Humans, Kinetics, Molecular Docking Simulation, Protein Binding, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors metabolism, Protein Structure, Tertiary, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Recombinant Proteins genetics, Structure-Activity Relationship, Casein Kinase II antagonists & inhibitors, Flavones chemistry, Protein Kinase Inhibitors chemistry
Abstract

Human protein kinase CK2 is one of the most intriguing enzymes, which functional role still remains unclear despite of decades of studying. At present there is abundant evidence pointing to the fact that inhibitors of CK2 could be used as pharmaceutical agents to treat cancer, viral infections and inflammatory diseases. Here we report novel synthetic flavone inhibitors, 4'-hydroxyflavones, possessing high activity towards CK2. These compounds were identified with receptor-based virtual screening and then chemically optimized on the base of rationale derived from biochemical screening and molecular modeling. It has been demonstrated that synthetic flavone derivatives are much more potent CK2 inhibitors than the natural ones, and we believe that their further examination will be helpful for studying biological role of CK2 as well as for development of new kinase-oriented drugs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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