灵芝羊毛甾烷型三萜抗肿瘤构效关系初探

多篇文献报道灵芝三萜具有良好的抗肿瘤活性,但其构效关系和作用靶点尚未系统比较。本研究以45种灵芝三萜为研究对象,通过对小鼠白血病细胞L1210的增殖抑制测定,来评价化合物抗肿瘤的能力。结果表明,灵芝菌丝体三萜和子实体中性三萜的活性较强。进一步采用Discovery Studio分子对接技术探讨了12种活性较强的灵芝三萜与5种抗肿瘤作用相关蛋白p53、Bcl-xl、EGFR、IL-2和VEGFR2之间可能的作用靶点,推测三萜化合物抗肿瘤能力与其结构上的乙酰氧基和母环上的共轭双键有关。其中,具有这一特征的含有3个乙酰氧基的ganoderic acid T,其抗肿瘤活性最强。本研究为灵芝三萜活性位点的寻找和结构改造提供了参考。

A preliminary investigation on anti-tumor structure-activity relationship of lanostane triterpenes from Ganoderma spp.

Several papers have reported that triterpenes from Ganoderma spp. have good antitumor activities, but their structure-activity relationships and targets of action have not been compared systematically. In this study, 45 lanostane triterpenes were investigated to evaluate the inhibition ability to mouse leukemia cells L1210’s proliferation. The results showed that neutral triterpene fractions from fruiting bodies of Ganoderma lingzhi and triterpenes isolated from mycelia of Ganoderma lingzhi were more active. The Discovery Studio molecular docking technique was further employed to explore the possible targets of action between twelve active triterpenes and the five antitumor effect-related proteins p53, Bcl-xl, EGFR, IL-2 and VEGFR2. It was hypothesized that the antitumor ability of the triterpenes was related to acetoxy groups and conjugated double bonds on the parent ring. Among them, ganoderic acid T which contains three acetoxy groups with this feature has the strongest antitumor activity. The study provides a useful reference for active site discovery and structural modification of lanostane triterpenes.