Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in the metabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail.
Keywords: active site; comparative molecular field analysis (CoMFA); comparative molecular similarity index analysis (CoMSIA); competitive inhibition; coumarins; cytochrome P450; docking; hologram quantitative structure-activity relationship (HQSAR); molecular modeling; quantitative structure-activity relationship (QSAR); time-dependent inhibition.