马拉巴酮C的大鼠肝微粒体生物转化及其体外对人胃癌细胞株的细胞毒活性研究

马拉巴酮C是从中药肉豆蔻（Myristicafragrans Hour．的种子）中提取到的，肉豆蔻科植物所特有的一类二芳基壬烷类化合物。本文首次利用大鼠肝微粒体对其进行了生物转化研究，明确其主要生物转化产物为马拉巴酮B。在体外对人胃癌细胞株NCI-N87和MGc803细胞毒活性评价试验中发现，原型化合物马拉巴酮C及其生物转化产物马拉巴酮B均具有与阳性药长春瑞滨相当的细胞毒活性。两者的半数抑制浓度，对NCI-N87细胞株分别为（42．62±3．10）和（19．80±1．70）μg／mL；对MGC803细胞株分别为（22．94±1．33）和（19．60±2．21）μg／mL。统计学分析表明，转化产物马拉巴酮B的细胞毒活性显著性强于原型化合物马拉巴酮C（对NCI-N87细胞P〈0．01，对MGC803细胞P〈0．05），提示肝微粒体对马拉巴酮C有活化作用。马拉巴酮C在肝微粒体的生物转化途径较为单一：马拉巴酮B和C具有治疗胃癌的开发潜力。

Biotransformation of malabaricone C by rat hepatic microsomes and cytotoxic activities against gastric cancer cells in vitro

Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investigated using rat hepatic microsomes for the first time and the main biotransformation product was elucidated as malabaricone B （2） according to the spectroscopic data. Further evaluation on human gastric cancer cell lines showed that the cytotoxic effects of malabaricone C and its metabolite malabaricone B were comparable to those of vinorelbine, with the values of IC50 of （42.62±3.10） and （19.80±1.70） μg/mL on NCI-N87, and （22.94±1.33） and （19.60±2.21） μg/mL on MGC803, respectively. Statistical analysis revealed that malabaricone B had significantly stronger cytotoxicity than the parent compound （P〈0.01 on NCI-N87 and P〈0.05 on MGC803）, which may indicate a bioactivation of malabaricone C by hepatic microsomes. These results suggest that malabaricone C has a simple biotransformation pathway by hepatic microsomes and provide valuable information for further investigation on both the parent compound and its biotransformation product as anti-gastric cancer agents or lead compounds.