General Research InterestSynthesis of Retinoids for Chemoprevention/Chemotherapy
Research DescriptionThe major thrust of my vitamin A-related research which has been built around the design, synthesis and use of stable analogs of unstable metabolites of vitamin A metabolites and vitamin A analogs (retinoids) to indirectly probe the role and biological activity of these parent, unstable metabolites. Typically, glucuronide conjugates of drugs and xenobiotics are assumed to be polar, excretory metabolites of the parent molecules. With the possible exception of the 6-O-glucuronide of morphine, few glucuronide conjugates have been shown to be biologically active species with any certainty. We are establishing that unhydrolyzable analogs of glucuronide conjugates of the semisynthetic retinoid 4-HPR are more potent, less toxic breast cancer preventive and therapeutic agents than the parent retinoids with virtual elimination of the teratogenic liability of this class of compounds.
Transinstitutional WorkWe have had a longstanding collaboration with Professor Hussein Abou-Issa (deceased) of Ohio State’s Department of Surgery. This collaboration on animal studies of our synthetic retinoid compounds in carcinogen treated rats has been continued with Dr. Galal Alshafie in Ohio State’s Department of Radiology. Our studies on the mechanism of action of our analogs and their teratogenicity are conducted in collaboration with Professor Margaret Clagett-Dame of the Department of Biochemistry of the University of Wisconsin-Madison.
We have a new collaboration evolving with Professors Earl Harrison of Ohio State’s Department of Nutrition and Steven Schwartz of Ohio State’s Department of Food Science. In these studies we are exploring the occurrence and significance of metabolites of $-carotene and lycopene with a particular emphasis on their impact on carcinogenicity. Our primary role in these studies is the synthesis and structural analysis of putative metabolites of the parent carotenoids.