Catalytic approach to metabolism of atractylenolide III using biomimetic iron-porphyrin complexes.

Atractylenolide III (AT-III) is a pharmacologically effective phytochemical and is known to be oxygenated during systemic metabolism mainly by cytochrome P450 enzymes (CYP450s), iron-containing porphyrin-based oxygenases. In rat plasma samples, the oxygenated metabolite of orally ingested AT-III was determined using liquid chromatography/mass spectrometry and the oxygenated form of AT-III was maintained at higher levels than the original form of AT-III. catalytic reactions using the iron(iv)-oxo porphyrin π-cation radical complex, [(tmp˙)Fe(O)], demonstrated that both H-atom abstraction and an oxygen rebound mechanism participated in the oxygenation process of AT-III. Density functional theory (DFT) confirmed the oxidative transformation occurred at the 4th and 10th carbon positions of AT-III. Co-treatment with acetaminophen had different effects between and models of AT-III metabolism. AT-III was metabolized an oxygenation process in the rat body, where CYP450 and other O-activating metalloenzymes might participate in the metabolism. The present work provided the oxidative metabolism of AT-III using an model parallel with biomimetic reaction models.