文章基本信息

标题：Polypharmacology of Gongronema latifolium leaf secondary metabolites against protein kinases implicated in Parkinson's disease and Alzheimer's disease
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作者：Babatunji Emmanuel Oyinloye ; Opeyemi Iwaloye ; Basiru Olaitan Ajiboye 等
期刊名称：Scientific African
印刷版ISSN：2468-2276
出版年度：2021
卷号：12
页码：1-9
DOI：10.1016/j.sciaf.2021.e00826
语种：English
出版社：Elsevier
摘要：Neurodegenerative diseases (NDD) are one of the major health concerns around the globe; Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most prevalent form of NDD. Protein kinases (PKs), common protein domains implicated in neurodegenerative diseases, are regulatory protein of cell functions; and play a pivotal role in signal transduction. Hence, this study considered the computational screening of secondary metabolites form Gongronema latifolium leaf for their inhibitory activities against the three prevalent PKs leucine-rich repeat kinase 2 (LRRK2), GSK3β (glycogen kinase 3β) and MAPK14 associated with the onset of AD and PD. The compounds were initially screened against LRRK2, GSK3β and MAPK14 by molecular docking to retrieve the hits. Nine (9) compounds were chosen and calculated for binding free energy to determine their stability with the proteins. The Lipinski, Ghose, Veber and Egan rules were considered to predict the compounds drug-likeness, in addition to drug-drug interaction and GI absorption. 2D QSAR models were constructed using a Kernel-based PLS regression model with Canvas binary fingerprint as the X variable. From the selected nine-hit with favourable stability with the proteins, 4 flavonoids (Catechin, Gallocatechin, Butein and Isorhamnetin) showed druglikeness attributes with a low tendency for drug-drug interaction and high GI absorption. The generated QSAR models also predicted moderate pIC50 values for these compounds against the three PKs. This study will help in future endeavours for finding effective therapy for AD and PD.
关键词：Neurodegenerative diseases Gongronema latifolium leaf LRRK2 GSK3β MAPK14 Molecular studies