In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions
Abstract Background The resistance of V600E-BRAF to the vemurafenib and the side effects of the identified inhibitors trigger the research for a novel and more potent anti-melanoma agents. In this study, virtual docking screening along with pharmacokinetics ADMET and drug-likeness predictions were c...
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doaj-4fafdb88d5a0451fba1bca7cc0bf730f2020-11-25T03:54:38ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532020-09-016111010.1186/s43094-020-00084-4In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictionsAbdullahi Bello Umar0Adamu Uzairu1Gideon Adamu Shallangwa2Sani Uba3Department of Chemistry, Faculty of Physical Sciences, Ahmad Bello UniversityDepartment of Chemistry, Faculty of Physical Sciences, Ahmad Bello UniversityDepartment of Chemistry, Faculty of Physical Sciences, Ahmad Bello UniversityDepartment of Chemistry, Faculty of Physical Sciences, Ahmad Bello UniversityAbstract Background The resistance of V600E-BRAF to the vemurafenib and the side effects of the identified inhibitors trigger the research for a novel and more potent anti-melanoma agents. In this study, virtual docking screening along with pharmacokinetics ADMET and drug-likeness predictions were combined to evaluate some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors. Results Some of the selected compounds exhibited better binding scores and favorable interaction with the V600E-BRAF enzyme. Out of the screened compounds, two most potent (5 and 9) having good Rerank scores (− 128.011 and − 126.258) emerged as effective and potent V600E-BRAF inhibitors that outperformed the FDA-approved V600E-BRAF inhibitor (vemurafenib, − 118.607). Thus, the molecular docking studies revealed that the studied compounds showed competing for inhibition of V600E-BRAF with vemurafenib at the binding site and possessed better pharmacological parameters based on the drug-likeness rules filters for the oral bioavailability, and ADMET risk parameters. Conclusion The docking analysis, drug-likeness rules filters, and ADMET study identified compounds (5 and 9) as the best hits against V600E-BRAF kinase with enhanced pharmacological properties. This recommends that these compounds may be developed as potent anti-melanoma agents.http://link.springer.com/article/10.1186/s43094-020-00084-4PyrimidinesV600E-BRAFMolecular dockingADMET |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Abdullahi Bello Umar Adamu Uzairu Gideon Adamu Shallangwa Sani Uba |
spellingShingle |
Abdullahi Bello Umar Adamu Uzairu Gideon Adamu Shallangwa Sani Uba In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions Future Journal of Pharmaceutical Sciences Pyrimidines V600E-BRAF Molecular docking ADMET |
author_facet |
Abdullahi Bello Umar Adamu Uzairu Gideon Adamu Shallangwa Sani Uba |
author_sort |
Abdullahi Bello Umar |
title |
In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions |
title_short |
In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions |
title_full |
In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions |
title_fullStr |
In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions |
title_full_unstemmed |
In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions |
title_sort |
in silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent v600e-braf inhibitors with pharmacokinetics admet and drug-likeness predictions |
publisher |
SpringerOpen |
series |
Future Journal of Pharmaceutical Sciences |
issn |
2314-7253 |
publishDate |
2020-09-01 |
description |
Abstract Background The resistance of V600E-BRAF to the vemurafenib and the side effects of the identified inhibitors trigger the research for a novel and more potent anti-melanoma agents. In this study, virtual docking screening along with pharmacokinetics ADMET and drug-likeness predictions were combined to evaluate some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors. Results Some of the selected compounds exhibited better binding scores and favorable interaction with the V600E-BRAF enzyme. Out of the screened compounds, two most potent (5 and 9) having good Rerank scores (− 128.011 and − 126.258) emerged as effective and potent V600E-BRAF inhibitors that outperformed the FDA-approved V600E-BRAF inhibitor (vemurafenib, − 118.607). Thus, the molecular docking studies revealed that the studied compounds showed competing for inhibition of V600E-BRAF with vemurafenib at the binding site and possessed better pharmacological parameters based on the drug-likeness rules filters for the oral bioavailability, and ADMET risk parameters. Conclusion The docking analysis, drug-likeness rules filters, and ADMET study identified compounds (5 and 9) as the best hits against V600E-BRAF kinase with enhanced pharmacological properties. This recommends that these compounds may be developed as potent anti-melanoma agents. |
topic |
Pyrimidines V600E-BRAF Molecular docking ADMET |
url |
http://link.springer.com/article/10.1186/s43094-020-00084-4 |
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