积雪草酸衍生物的合成及体外抗肿瘤活性的研究

Synthesis of Asiatic Acid Derivatives and Study on Anti-tumor Activity in Vitro

以天然产物积雪草酸(AA)为母体设计并合成新的积雪草酸衍生物,并进行体外抗肿瘤活性实验和分子对接研究.以积雪草酸为原料,对其A环及28位羧基进行结构改造,合成4个新的积雪草酸衍生物.采用MTT法,选用人癌细胞SGC7901和A549进行初步的体外抗肿瘤活性研究;并进行分子对接实验,研究化合物与Bcl-xL受体之间的作用.结果表明:合成了4个未见文献报道的新型积雪草酸衍生物,其结构经过^(1)H-NMR、^(13)C-NMR和HR-MS确证.所有目标化合物对A549和SGC7901细胞增殖的抑制作用均优于母体积雪草酸.其中化合物Ⅰ_(3)抗肿瘤活性与阳性对照药Navitoclax相当;分子对接结果显示Ⅰ_(3)与Bcl-xL受体具有较好的结合能力.化合物Ⅰ_(3)具有较好的抗肿瘤活性,值得进一步研究.

A new asiatic acid derivative was designed and synthesized from natural asiatic acid(AA),and its antitumor activity in vitro and molecular docking were studied.Four new asiatic acid derivatives were synthesized from asiatic acid by structural modification of its A-ring and 28 carboxyl group.Using MTT method,human cancer cells SGC7901 and A549 were selected for preliminary in vitro antitumor activity study,and molecular docking experiments were carried out to study the interaction between the compound and Bcl-xL receptor.The results showed that four new asiatic acid derivatives were synthesized and their structures were confirmed by^(1)H-NMR,^(13)C-NMR and HR-MS.The inhibitory effects of all target compounds on the proliferation of A549 and SGC7901 cells were better than that of mother volume snow oxalic acid.Among them,the antitumor activity of compound I_(3) was equivalent to that of the positive control drug navitoclax.The results of molecular docking showed that compound I_(3) had good binding ability with Bcl-xL receptor.Compound I_(3) has good antitumor activity and deserves further study.