Development of the anti-cancer promoting activity prediction method for the quinones which assume oxidation-reduction potential as a key parameter

点击翻译按钮获取中文摘要

The oxidation-reduction potential as a parameter for analysis was evaluated on the basis of suggesting a generality to the correlation between the inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation and oxidation-reduction potentials for quinones. Based on this result, a reliable evaluation of the anti-tumor activity of quinone derivatives can be made by measuring their reduction potentials, without in vitro screening. 11 Polyhydroxyanthraquinones and 8 O-methylemodin derivatives were synthesized and natural anthraquinones, such as obutusin, were isolated from cassia seed to organize the fundamental data. In addition, we have developed a simple and rapid high-performance liquid chromatography method to separate and determine anthraquinones, such as emodin, in rhubarb. We examined the correlations between the inhibitory effects on EBV-EA activation and oxidation-reduction potentials about these obtained compounds. As a result, it was found that the first reduction potential at a physiological pH correlated with the inhibitory effects of hydroxy and/or methoxy polysubstituted anthraquinones on EBV-EA activation and could be a useful parameter as a prediction method of the anti-tumor promoting effects.As 1-azaanthraquinone had the same correlation as anthraquinones, we synthesized heteroquinones including oxygen, nitrogen and/or sulfur atoms in the rings, and examined the oxidation-reduction potential of these heteroquinones using cyclic voltammetry. Then, we investigated the correlations between the potentials and inhibitory effects of cancer cell growth or lethal effect of heteroquinones, so that we found good correlations about the effects of activity and the first reduction potentials. Thus, the first reduction potential seems to be promising parameter for predicting the biological activity as anthraquinones.Furthermore, it was clarified that the metabolites of emodin in Raji cells were 8-O-methylemodin and orhydroxy-emodin by LC/APCI-MS.