title: Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors.
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.
authors.affiliation: Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore- 570006, India.
authors.lastname: Chandra
authors.affiliation: Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore- 570006, India ; Department of Studies in Biochemistry, Manasagangotri, University of Mysore, Mysore- 570006, India.
authors.forename: Vishalakshi Gopalapura
authors.initials: VG
authors.lastname: Javaregowda
authors.affiliation: Department of Physics, SJB Institute of Technology, Kengeri, Bangalore 560060, India.
authors.forename: Beeranahally Haruvegowda
authors.initials: BH
authors.lastname: Doreswamy
authors.affiliation: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore-560005, India.
authors.forename: Srikantamurthy
authors.initials: S
authors.lastname: Ningaiah
authors.affiliation: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore-560005, India.
authors.forename: Umesha K
authors.initials: UK
authors.lastname: Bhadraiah
authors.affiliation: Department of Studies in Biochemistry, Manasagangotri, University of Mysore, Mysore- 570006, India.
authors.forename: Kempaiah
authors.initials: K
authors.lastname: Kemparaju
authors.affiliation: Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore- 570006, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Madegowda
keywords: Docking studies; Protein kinases inhibitors; Pyrazole derivatives; Tyrosine kinase receptor