Virtual Screening and Molecular Docking of Flavone Derivatives as a Potential Anticancer Drug in the Presence of Dexamethasone

CDK6 is a pivotal kinase in cell cycle progression and has been targeted in many cancers and degenerative diseases. Fisetin, a potent flavonol inhibitor of CDK6, was modified in silico to develop better CDK6 inhibitor(s). Molecular docking studies were performed with in silico-derived fisetin derivatives. All fisetin derivatives were capable of being CDK6 inhibitors; two of them had improved binding characteristics compared to fisetin. Molecular docking studies were executed in the presence of dexamethasone, a commonly administered corticosteroid. These two derivatives showed a stronger binding affinity with CDK6 in the presence of dexamethasone. Two fisetin derivatives had a thermodynamically favorable interaction with CDK6 compared to fisetin and had equivalent ADME properties, and would be well tolerated by the body. This study holds immense potential for developing new flavonoid drugs for cancer.