Anticancer screening of medicinal plant phytochemicals against Cyclin-Dependent Kinase-2 (CDK2): An in-silico approach

Wajahat Khan, Usman Ali Ashfaq, Sadia Aslam, Sidra Saif, Tehzeeb Aslam, Kishver Tusleem, Arooma Maryam, Muhammad Tahir ul Qamar


Background: Cyclin-Dependent Kinase-2 (CDK2) is a member of serine/threonine protein kinases family and plays an important role in regulation of various eukaryotic cell division events. Over-expression of CDK2 during cell cycle may lead to several cellular functional aberrations including diverse types of cancers (lung cancer, primary colorectal carcinoma, ovarian cancer, melanoma and pancreatic carcinoma) in humans. Medicinal plants phytochemicals which have anticancer potential can be used as an alternative drug resource.

Methods: This study was designed to find out anticancer phytochemicals from medicinal plants which could inhibit CDK2 with the help of molecular docking technique. Molecular Operating Environment (MOE v2009) software was used to dock 2300 phytochemicals in this study.

Results: The outcome of this study shows that four phytochemicals Kushenol T, Remangiflavanone B, Neocalyxins A and Elenoside showed the lowest S-score (-17.83, -17.57, -17.26, -17.17 respectively) and binds strongly with all eight active residues Tyr15, Lys33, Ileu52, Lys56, Leu78, phe80, Asp145 and Phe146 of CDK2 binding site. These phytochemicals could successfully inhibit the CDK2.

Conclusion: These phytochemicals can be considered as potential anticancer agents and used in drug development against CDK2. We anticipate that this study would pave way for phytochemical based novel small molecules as more efficacious and selective anti-cancer therapeutic compounds.

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