齐墩果酸-苯甲醛缀合物的合成及抗肿瘤活性研究

Synthesis and anti-tumor activity evaluation of oleanolic acid-benzaldehyde conjugate

以天然产物齐墩果酸为起始原料,将苯甲醛通过酯化反应拼接到齐墩果酸的C28位,合成了齐墩果酸-苯甲醛缀合物,其结构通过1H NMR进行了确证。同时,探讨了不同酯化反应条件对产率收率的影响。确定了最佳反应条件为:物料比nDMAP∶nEDC∶nOA=0.5∶5∶1、反应时间为24h,缀合物的产率最高。随后,通过初步的活性测试结果表明,齐墩果酸-苯甲醛缀合物对HepG2、MCF-7、PC3和HeLa均有明显的抑制活性,并强于先导化合物齐墩果酸和苯甲醛;此外,齐墩果酸-苯甲醛缀合物对正常的MCF-10A细胞没有毒性。

Oleanolic acid-benzaldehyde conjugate was synthesized via esterification at C28 of oleanolic acid using the natural oleanolic acid as starting material. The structure of this conjugate was confirmed by 1H NMR. Moreover, the effect of different esterification conditions on yield of the conjugate was discussed. The optimum reaction conditions were determined as follows: nDMAP∶nEDC∶nOA was 0.5∶5∶1;the reaction time was 24 h, and the yield of conjugates was the highest. Subsequently, anti-tumor activities of oleanolic acid-benzaldehyde conjugate were evaluated, against HepG2, MCF-7, PC3 and HeLa cell lines in vitro. The preliminary biological results showed that oleanolic acid-benzaldehyde conjugate displayed obvious antiproliferative effect on HepG2, MCF-7, PC3 and HeLa,which was stronger than oleanolic acid and benzaldehyde. Additionally, oleanolic acid-benzaldehyde conjugate was nontoxicity to normal MCF-10A cells.