Dr. Mark Janik's Research Group

      My research focus as well as that of my research group lies in the areas of synthetic organic and medicinal chemistry. Specifically, we are interested in further exploring the binding of the anticancer compound colchicine 1 (Figure 1) with the protein tubulin. Structurally, colchicine consists of a three ringed system: a trimethoxybenzene ring (A ring), a saturated seven membered ring containing an acetamido group (B ring), and an ?-methoxytropone ring (C ring). Besides colchicine, many molecules that bind to the colchicine domain of tubulin have also been highly investigated. One such compound is 2-methoxy-5-(2´,3´,4´-trimethoxyphenyl) tropone 2 (MTC, Figure 1), a bicyclic colchicinoid that lacks the central B ring of the parent compound colchicine. The compound MTC is nearly as potent as colchicine and it binds to tubulin at the colchicine binding site. However, despite this high potency, compounds such as colchicine and MTC are not yet in standard use as anticancer agents.

      Attempts to obtain potent colchicine site analogs have typically focused on using conventional structure-activity relationship (SAR) studies. In addition, many of these SAR studies have also sought to further clarify the mechanistic understanding of the colchicine-tubulin interaction with the hope that this would produce more clinically useful colchicine site drugs. With this in mind, our group has focused on synthesizing both colchicine and MTC analogs that will be used in SAR studies. These analogs will potentially shed additional light on the colchicine-tubulin interaction. More importantly, the information obtained from these studies may provide new leads in cancer chemotherapy.