Research Projects

Cyclin-dependent kinases (CDKs) are serine-threonine kinases that play a significant role in cell cycle regulation and are attractive therapeutic targets. Many CDK inhibitors (CDKIs) have been approved as drugs to treat various types of cancers, with two major categories: selective CDKIs and pan-CDKIs. A previous study showed naturally occurring flavone alkaloid, rohitukine, as a potent CDK inhibitor: IIIM-290. This study rationally replaced the flavone and chromone core with coumarin and phenylcoumarin and proposed a series of novel molecules to discover potent CDKIs. Various coumarins have shown potent cytotoxicity and anti-cancer potential in various studies. Most flavone-containing CDKI (alvocidib) exert their mechanism by occupying ATP binding pockets. Further substitution significantly affects the interaction of ligand with CDKs. The rational replacement of flavone by coumarin may lead to the discovery of potent CDKIs. Computational studies have been performed in support of typically designed compounds, and the docking score was good. The prime objective of the proposal is to design and prepare the novel series of coumarin derivatives, conduct in-vitro CDK-inhibition and cytotoxicity screening, and evaluate lead in an in-vivo model. The extended objective will be clinical studies in the future. The expected outcome is a new therapeutic product/lead molecule for cancer treatment.