We design, synthesize, and perform bioassays of potential inhibitors of cytochrome P450 enzymes, which are a superfamily of hemoproteins involved in metabolism and carcinogenesis. Previous studies in our lab have established that a number of aromatic acetylenes are selective suicide inhibitors of cytochrome P450-dependent monooxygenases. Due to the special properties of suicide inhibitors, these compounds are useful tools in the studies of cancer development and treatment. Additionally, the mechanism of action of these inhibitors makes it possible to use them as probes into the active sites of P450 enzymes leading to better understanding of the structure-activity relationships involved in the P450-dependent reactions; and to use the newly synthesized compounds as experimental tools in investigating the role of these P450 enzymes in the carcinogenesis process.
In recent years, breast cancer researchers have increasingly focused on the regulation of sphingolipid metabolism which has been shown to be closely related to cancer pathogenesis and drug resistance. Ceramide (the central molecule of sphingolipid pathway) regulation and metabolism were proved to be novel targets for anti-cancer drug design. Our group designs and synthesizes ceramide analogs as potential treatment for chemo- and endocrine-resistant breasts cancers. The anti-cancer activity of our novel analogs on breast cancer cell lines are studied by our collaborators at Tulane University.
