Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors

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Title	Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors
Authors	Chandra¹, Vishalakshi Gopalapura Javaregowda^1,2, Beeranahally Haruvegowda Doreswamy³, Srikantamurthy Ningaiah⁴, Umesha K Bhadraiah⁴, Kempaiah Kemparaju² & Mahendra Madegowda¹*
Affiliation	¹Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore- 570006, India; ²Department of Studies in Biochemistry, Manasagangotri, University of Mysore, Mysore- 570006, India; ³Department of Physics, SJB Institute of Technology, Kengeri, Bangalore 560060, India; ⁴Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore-560005, India
Email	mahendra@physics.uni-mysore.ac.in; *Corresponding author
Article Type	Hypothesis
Date	Received April 20, 2014; Accepted June 24, 2014; Published July 22, 2014
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.
Keywords	Pyrazole derivatives, Tyrosine kinase receptor, Protein kinases inhibitors, Docking studies.
Citation	Chandra et al. Bioinformation 10(7): 413-418 (2014)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.