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标题：In silico binding affinity studies of N-9 substituted 6-(4-(4-propoxyphenyl)piperazin-1-yl)-9H-purine derivatives-Target for P70-S6K1 & PI3K-δ kinases
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作者：Manjunath G. Sunagar ; Manjunath G. Sunagar ; P. Aravind 等
期刊名称：Beni-Suef University Journal of Basic and Applied Sciences
印刷版ISSN：2314-8535
电子版ISSN：2314-8543
出版年度：2018
卷号：7
期号：1
页码：84-91
DOI：10.1016/j.bjbas.2017.08.004
语种：English
出版社：Elsevier
摘要：Graphical abstractDisplay OmittedHighlights•in silicostudy of purine ligands for their binding affinity with P70-S6K1 & PI3K-δ.•PP16 with highest binding affinity for both kinases compared to the standard ligands.•N-9 coumarine substituted purine derivative as potential inhibitor of both kinases.AbstractP70-S6K1 & PI3K-δ kinases are identified to be involved in many physiological processes associated with cancer, therefore many of the inhibitors being designed to target these kinases are in clinical trials. In the current study we have exploited the N-9 substituted 6-(4-(4-propoxyphenyl) piperazin-1-yl)-9H-purine derivatives for their inhibitory properties with the above kinases. We have used anin silicodocking study with seventeen purine derivatives for their binding affinity calculations. The binding affinities of these small molecules with P70-S6K1 & PI3K-δ were performed using AutoDock Vina. Among all the compounds, PP16 showed highest binding affinity of −14.7kcal/mol with P70-S6K1 kinase & −17.2kcal/mol with PI3K-δ kinases as compared to the molecules under clinical trials (PF-4708671 & IC-87114). Docking studies revealed that N-9 coumarine substituted purine derivative could be one of the potential ligands for the inhibition of P70-S6K1 & PI3K-δ kinases. Hence, this compound can be further investigated byin vitroandin vivoexperiments for further validation.
关键词：Kinase;Binding affinity;In silico;Purine;P70-S6K1;PI3K-δ