人参皂苷Rh2辛酸单酯的合成及其抗肿瘤活性研究

Synthesis and anti-tumor activity of ginsenoside Rh2 caprylic acid monoester

由于人参皂苷Rh2的生物利用度极低且对人体正常细胞具有毒性,因此设计和优化人参皂苷Rh2结构是提高其抗肿瘤活性和降低毒性的关键。通过辛酰氯与人参皂苷Rh2反应,合成了1种新的酯衍生物辛酸单酯(C-Rh2)。用一维核磁共振和二维核磁共振以及电喷雾电离质谱等技术对新型人参皂苷衍生物的结构进行了结构鉴定。探索了C-Rh2对H22荷瘤小鼠的抗肿瘤活性。C-Rh2具有一定的抗肿瘤活性,且与Rh2相比,毒性降低。C-Rh2作为人参皂苷Rh2的脂肪酸酯,具有一定的抗肿瘤活性和较低的毒性,但其具体作用机制有待进一步研究。

Ginsenoside Rh2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh2 possessed variety of activities,but bioavailability of oral administration Rh2 was extremely low due to poor absorption. Moreover,ginsenoside Rh2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh2 named caprylic acid monoester of Rh2( C-Rh2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh2 was tested on H22 tumor bearing mice. C-Rh2 displayed certain anti-tumor activities and exhibited less toxicity than Rh2. In the present study,C-Rh2 as ester form of ginsenoside Rh2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.