新型3-O-乙酰-11-酮基-β-乳香酸衍生物的合成及其体外抗肿瘤活性

Synthesis of Novel 3-O-acetyl-11-keto-β-boswellic Acid Derivatives and In Vitro Anti-tumor Activities

以3-O-乙酰基-11-酮-β-乳香酸(AKBA)为原料,经过氯化、取代反应,合成了8个新型的AKBA酰胺类衍生物(S137、S151、S179、S184、S443、S634、S667和S673),其结构经^(1)H NMR和MS(ESI)表征。采用CCK8法测试了目标化合物对人原髓细胞白血病细胞(HL-60)、人结肠癌细胞(HCT116)和非小细胞肺癌细胞(A549)的体外抗肿瘤活性。结果表明:除S184和S443外,S137、S151、S179、S634、S667、S673对3种细胞株的活性均有一定的抑制作用,其中S137对HL-60和A549的抑制效果较好,IC_(50)分别为1.781和1.763μM,优于AKBA(IC_(50)=16.160和10.900μM);S151对HL-60抑制效果最好,IC_(50)为1.255μM,优于AKBA(IC_(50)=16.160μM);S634对HCT116的抑制效果最好,IC_(50)为1.193μM,优于AKBA(IC_(50)=13.020μM)。

Eight novel AKBA amide derivatives(S137,S151,S179,S184,S443,S634,S667 and S673)were synthesized from 3-acetyl-11-keto-β-boswellic acid(AKBA)by chlorination and substitution reaction.The target compounds were characterized by ^(1)H NMR and MS(ESI).The in vitro antitumor activities of these target compounds on human promyelocytic leukemia cell line(HL-60),human colon cancer cells(HCT116)and non-small cell lung cancer cells(A549)were tested by CCK8 method.The results showed that S137,S151,S179,S634,S667 and S673 inhibited the activity of these three cell lines except S184 and S443.Among them,S137 had a good inhibitory effect on HL-60 and A549,better than AKBA(IC_(50)=16.160 and 10.900μM),and IC_(50) were 1.781 and 1.763μM,respectively;S151 had the best inhibitory effect on HL-60,better than AKBA(IC_(50)=16.16μM),and IC_(50) was 1.255μM;S634 had the best inhibitory effect on HCT116 better than AKBA(IC_(50)=13.02μM),and IC_(50) was 1.193μM.