The major classes of anticancer drugs include antimetabolites, anthracyclines, taxanes and alkylating agents. They disrupt cell DNA, prevent DNA synthesis or target microtubules to stop cancer cells from dividing. These disruptions induce apoptosis to kill the cells. Acquired or intrinsic drug resistance and resistance to apoptotic cell death are one of the major reasons for our inability to cure cancer. In collaboration with Drs. Gilbert Arthur and Mark Nachtigal (Department of Biochemistry & Medical Genetics, UofM), we are working on glycolipid-based antitumor compounds that are able to kill cancer cells and cancer stem cells via a novel non-apoptotic mechanism. We recently discovered that glycosylated antitumor ether lipids (GAELs) possess high selectivity against ovarian cancer cells. We are currently performing systematic structure activity relationships and mode of action studies to develop potent metabolically stable analogs of this class of compounds for in vivo studies. The goal is to develop drug candidates that will be effective against ovarian cancers resistant to the current chemotherapeutic agents.
Selected Publications:
J. Med. Chem. 2017,
60, 2142-2147.
J. Med. Chem. 2017,
60, 9724-9738.
