Abstract
Cyclin-dependent kinase 6 (CDK6) is a potential drug target that plays an important role in the progression of different types of cancers. We performed in silico and in vitro screening of different natural compounds and found that quercetin has a high binding affinity for the CDK6 and inhibits its activity with an IC50 = 5.89 μM. Molecular docking and a 200 ns whole atom simulation of the CDK6-quercetin complex provide insights into the binding mechanism and stability of the complex. Binding parameters ascertained by fluorescence and isothermal titration calorimetry studies revealed a binding constant in the range of 107 M–1 of quercetin to the CDK6. Thermodynamic parameters associated with the formation of the CDK6–quercetin complex suggested an electrostatic interaction-driven process. The cell-based protein expression studies in the breast (MCF-7) and lung (A549) cancer cells revealed that the treatment of quercetin decreases the expression of CDK6. Quercetin also decreases the viability and colony formation potential of selected cancer cells. Moreover, quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression. Both in silico and in vitro studies highlight the significance of quercetin for the development of anticancer leads in terms of CDK6 inhibitors.