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Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Biomedical Informatics
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135288/ https://www.ncbi.nlm.nih.gov/pubmed/25187680 http://dx.doi.org/10.6026/97320630010413 |
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author | Chandra, Javaregowda, Vishalakshi Gopalapura Doreswamy, Beeranahally Haruvegowda Ningaiah, Srikantamurthy Bhadraiah, Umesha K Kemparaju, Kempaiah Madegowda, Mahendra |
author_facet | Chandra, Javaregowda, Vishalakshi Gopalapura Doreswamy, Beeranahally Haruvegowda Ningaiah, Srikantamurthy Bhadraiah, Umesha K Kemparaju, Kempaiah Madegowda, Mahendra |
author_sort | Chandra, |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4135288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Biomedical Informatics |
record_format | MEDLINE/PubMed |
spelling | pubmed-41352882014-09-03 Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors Chandra, Javaregowda, Vishalakshi Gopalapura Doreswamy, Beeranahally Haruvegowda Ningaiah, Srikantamurthy Bhadraiah, Umesha K Kemparaju, Kempaiah Madegowda, Mahendra Bioinformation Hypothesis 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. Biomedical Informatics 2014-07-22 /pmc/articles/PMC4135288/ /pubmed/25187680 http://dx.doi.org/10.6026/97320630010413 Text en © 2014 Biomedical Informatics This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited. |
spellingShingle | Hypothesis Chandra, Javaregowda, Vishalakshi Gopalapura Doreswamy, Beeranahally Haruvegowda Ningaiah, Srikantamurthy Bhadraiah, Umesha K Kemparaju, Kempaiah Madegowda, Mahendra Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
title | Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
title_full | Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
title_fullStr | Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
title_full_unstemmed | Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
title_short | Molecular docking of 1H-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
title_sort | molecular docking of 1h-pyrazole derivatives to receptor tyrosine kinase and protein kinase for screening potential inhibitors |
topic | Hypothesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135288/ https://www.ncbi.nlm.nih.gov/pubmed/25187680 http://dx.doi.org/10.6026/97320630010413 |
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