桦褐孔菌三萜的酰化对其抗肿瘤活性的影响

Synthesis of acylated triterpenes of Inonotus obliquus and their antitumor activities

关键词:  桦褐孔菌  三萜  酰化  抗肿瘤

Key words:  Inonotus obliquus  triterpene  acylation  antitumor

摘要:

[目的]考察桦褐孔菌中三萜化合物发生酰化成酯后对其抗肿瘤活性的影响。[方法]采用溶剂提取法及硅胶柱层析、ODS开放柱层析和制备型高效液相色谱（HPLC）等从桦褐孔菌子实体中分离制备其代表性羊毛脂烷型三萜，并以此为原料，采用琥珀酸酐进行酰化反应，进而采用噻唑蓝（MTT）法测试原料化合物及其酰化产物对A549、Hela、MCF-7及4T1肿瘤细胞的抑制活性。[结果]从桦褐孔菌中分离并鉴定了化合物inotodiol（1）、trametenolic acid（2）及inonotusane A（3），将他们进行酰化后分别得到inotodiol-3-琥珀酸单酯（1a）、inotodiol-22-琥珀酸单酯（1b）、inotodiol-3，22-琥珀酸二酯（1c）、trametenolic acid-3-琥珀酸单酯（2a）和inonotusane A-3-琥珀酸单酯（3a）。MTT结果表明，化合物1的3-位、22-位酰化后（1a，1b，1c）对A549和4T1肿瘤细胞的抑制活性均增强，此外，而其3-位酰化后（1a）还大大增强了对MCF-7肿瘤细胞的抑制活性。化合物2酰化后对活性无影响。化合物3的3-位酰化后对A549、MCF-7及4T1细胞的抑制活性均明显增强，其中对A549表现出最强的抗肿瘤活性（IC₅₀=9.53 μmol/L）。[结论]化合物inotodiol（1）的3-位、22-位和inonotusane A（3）的3-位酰化后均增强了其肿瘤活性，为其进一步的结构修饰提供了有价值的参考。

Abstract:

[Objective] To synthesize acylated triterpenes of Inonotus obliquus and study the effect of acylation on antitumor activity.[Methods] The triterpenes were separated from the 95% ethanol extracts of I. obliquus by silica gel, ODS column chromatograph and preparative HPLC. The compounds were then acylated with succinic anhydride. The antitumor activities of the triterpenes and their acetylation products against A549, Hela, MCF-7 and 4T1 cancer cells were tested by MTT method.[Results] Inotodiol (1), trametenolic acid (2) and inonotusane A (3) were isolated and identified from I. obliquus. They were acylated to inotodiol-3-mono succinate (1a), inotodiol-22-mono succinate (1b), inotodiol-3,22-di succinate (1c), trametenolic acid-3-mono succinate (2a) and inonotusane A-3-mono succinate (3a) respectively. MTT tests showed that the antitumor activities of 1a, 1b and 1c against A549 and 4T1 were stronger than 1. Furthermore, the antitumor activity of 1a against MCF-7 was stronger than 1. The antitumor activities of 3 against A549, MCF-7 and 4T1 were all enhanced after acylation. Activity of 3a against A549 was the strongest (with IC₅₀=9.53 μM). While neither 2 or 2a was inactive.[Conclusion] Acylation on 3-position or 22-position in 1 and 22-position in 3 enhance the anti-tumor activity. This provides valuable reference for their further structure modification.