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Keywords = Lupinisoflavone C

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13 pages, 4064 KB  
Article
Bioactive Phytoconstituents as Potent Inhibitors of Tyrosine-Protein Kinase Yes (YES1): Implications in Anticancer Therapeutics
by Chunmin Yang, Afsar Alam, Fahad A. Alhumaydhi, Mohd Shahnawaz Khan, Suliman A. Alsagaby, Waleed Al Abdulmonem, Md. Imtaiyaz Hassan, Anas Shamsi, Bilqees Bano and Dharmendra Kumar Yadav
Molecules 2022, 27(10), 3060; https://doi.org/10.3390/molecules27103060 - 10 May 2022
Cited by 24 | Viewed by 4220
Abstract
Tyrosine-protein kinase Yes (YES1) belongs to the Tyrosine-protein kinase family and is involved in several biological activities, including cell survival, cell–cell adhesion, cell differentiation, and cytoskeleton remodeling. It is highly expressed in esophageal, lung, and bladder cancers, and thus considered as an attractive [...] Read more.
Tyrosine-protein kinase Yes (YES1) belongs to the Tyrosine-protein kinase family and is involved in several biological activities, including cell survival, cell–cell adhesion, cell differentiation, and cytoskeleton remodeling. It is highly expressed in esophageal, lung, and bladder cancers, and thus considered as an attractive drug target for cancer therapy. In this study, we performed a virtual screening of phytoconstituents from the IMPPAT database to identify potential inhibitors of YES1. Initially, the molecules were retrieved on their physicochemical properties following the Lipinski rule of five. Then binding affinities calculation, PAINS filter, ADMET, and PASS analyses followed by an interaction analysis to select safe and clinically better hits. Finally, two compounds, Glabrene and Lupinisoflavone C (LIC), with appreciable affinities and a specific interaction towards the AlphaFold predicted structure of YES1, were identified. Their time-evolution analyses were carried out using an all-atom molecular dynamics (MD) simulation, principal component analysis, and free energy landscapes. Altogether, we propose that Glabrene and LIC can be further explored in clinical settings to develop anticancer therapeutics targeting YES1 kinase. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Asia)
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