Cytochrome P450s are a superfamily of heme-containing monooxygenase enzymes that are mainly responsible for the metabolism and detoxification of endogenous and xenobiotic substances. However, these versatile enzymes may also bioactivate procarcinogens into carcinogens. As a result, inhibiting family I P450 enzymes has become a target for cancer prevention and carcinogenesis studies. The project reported here focuses on the development and synthesis of selective inhibitors towards P450 family I enzymes 1A1 and 1A2. As part of a larger project, five novel coumarin derivatives were designed, synthesized, isolated, and structurally studied for use in <i>in vitro</i> P450 inhibition bioassays. Bioassays for P450 1A1 and 1A2 inhibition have been conducted on the synthesized coumarin derivatives. The derivatives reported here are 7,8-pyrano-4-phenylcoumarin (78P4PC), 7,8-furano-4-methylcoumarin (78F4MC), 7,8-pyrano-4-trifluorocoumarin (78P4TFC), 7,8-furano-4-trifluorocoumain (78F4TFC), and 7,8-dioxolo-4-phenylcoumarin (78DO4PC).

Synthesis of coumarin derivatives as potential inhibitors of human cytochrome P450 enzymes

249th National Meeting (2015)

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