Identification of Cytotoxic Dimers in Oxidation Product from Sesamol, a Potent Antioxidant of Sesame Oil

Phytophenols of edible plants have recently attracted much attention as potent antioxidants and related bioactive substances. These antioxidative phytophenols are very oxidizable due to their chemical properties, and their oxidation products must accumulate in the oxidizing foods when they are contained as active ingredients. In this investigation, several phytophenols, which are well known as potent antioxidants in food science, were oxidized by oxygen in the presence of a catalytic amount of Ferric ion. Caffeic acid, catechin, chlorogenic acid, rosmarinic acid, and sesamol were quickly oxidized, whereas eugenol, resveratrol, rutin, and quercetin were not under the stated conditions. The oxidation product mixtures of the quickly oxidized phytophenols were next subjected to a cytotoxic assay using normal cells. Among the products, the oxidation product from sesamol showed a remarkably high cytotoxic activity. To clarify the cytotoxic principle of the oxidation products, an assay-guided fractionation and subsequent isolation of the oxidation compound of sesamol was carried out. Structure analysis of the isolated compounds revealed that they are new dimeric compounds (2-5) of sesamol. The cytotoxic activity of the dimers was evaluated from the population of dead cells by a flow cytometric analysis of rat thymocytes in the presence of 100 mu M of each compound. Compound 2 showed the most potent cytotoxic activity among them. Compound 2 has a typical conjugated carbonyl moiety and the moiety possibly contributes to its high toxicity from a structure activity point of view.