Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
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Authors: | Chandra Vishalakshi Gopalapura Javaregowda Beeranahally Haruvegowda Doreswamy Srikantamurthy Ningaiah Umesha K Bhadraiah Kempaiah Kemparaju Mahendra Madegowda |
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Institution: | 1.Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore- 570006, India;2.Department of Studies in Biochemistry, Manasagangotri, University of Mysore, Mysore- 570006, India;3.Department of Physics, SJB Institute of Technology, Kengeri, Bangalore 560060, India;4.Department of Chemistry, Yuvaraja''s College, University of Mysore, Mysore-560005, India |
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Abstract: | Tyrosine kinase receptor and protein kinases drawn much attention for the scientific fraternity in drug discovery due to its
important role in different cancer, cardiovascular diseases and other hyper-proliferative disorders. Docking studies of pyrazole
derivatives with tyrosine kinase and different serine/threonine protein kinases were employed by using flexible ligand docking
approach of AutoDock 4.2. Among the molecules tested for docking study, 2-(4-chlorophenyl)-5-(3-(4-chlorophenyl)-5-methyl-1-
phenyl-1H-pyrazol-4-yl)-1,3,4-thiadiazole (1b), 2-(4-methoxyphenyl)-5-(3-(4-methoxyphenyl)-5-methyl-1-phenyl-1H-pyrazol-4-yl)-
1,3,4-thiadiazole (1d) and 2-(4-chlorophenyl)-5-(3-(4-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazol-4-yl)-1,3,4-thiadiazole (2b)
revealed minimum binding energy of -10.09, -8.57 and -10.35 kJ/mol with VEGFR-2 (2QU5), Aurora A (2W1G) and CDK2 (2VTO)
protein targets, respectively. These proteins are representatives of plausible models of interactions with different anticancer agents.
All the ligands were docked deeply within the binding pocket region of all the three proteins, showing reasonable hydrogen bonds.
The docking study results showed that these pyrazole derivatives are potential inhibitor of all the three protein targets; and also all
these docked compounds have good inhibition constant, vdW + Hbond + desolv energy with best RMSD value. |
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Keywords: | Pyrazole derivatives Tyrosine kinase receptor Protein kinases inhibitors Docking studies |
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