In silico analysis and molecular docking studies of mannich base Lawsone derivatives functionalized ZnO nanocomposites (LSDs) against BRAF and CDK4 proteins

Cyclin-dependent kinase 4 (CDK4) is a potent anti-cancer therapeutic target because of its role in cell proliferation. BRAF is the most important member of the RAF kinases family. 66% of melanomas and 7% of all cancers have been found to have BRAF mutations. Therefore, selective inhibition of CDK4 and BRAF may enhance therapeutic efficacy. The Lawsone derived Mannich base functionalized ZnO nanocomposites (LM@ZnO) have been successfully synthesized. To apprehend the LM@ZnO as an antitumor agent, we have performed in silico studies against BRAF and CDK4 proteins. Molecular docking studies of all LM@ZnO revealed greater binding energy when compared to the standard drug doxorubicin which displayed -110.6 and -107.212 kcal/mol against CDK4 and BRAF proteins respectively. This study validates that anticancer efficacy is not always dependent on antioxidant activity; there could be another mechanism that leads to cell growth suppression during the cell cycle.