18β-甘草次酸类衍生物的设计、合成及抑制肿瘤细胞增殖活性

Design,synthesis and antiproliferative activity in cancer cells of novel 18β-glycyrrhetinic acid derivatives

以18β-甘草次酸为先导化合物,考察18β-甘草次酸中C环双键位置对抗肿瘤活性的影响,设计一系列含9(11)-烯结构的衍生物,以期提高该类化合物的抗肿瘤作用。合成了23个未见文献报道的化合物,结构均经IR、LC-MS和1H NMR确证。以18β-甘草次酸为阳性对照,采用MTT法考察了24个目标化合物对人前列腺癌细胞PC-3的生长抑制活性,并采用细胞计数法测定了12个化合物对人急性早幼粒白细胞HL-60的生长抑制作用。活性结果表明,部分目标化合物的生长抑制活性优于母体,尤以化合物14的活性最强,对PC-3细胞及HL-60细胞的GI50分别为4.48μmol·L-1和1.2μmol·L-1,值得深入研究。

To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid （GA）, a series of GA derivatives featured with 9（11）-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects tOwards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GIs0 values of 4.48 μmol·L-1 and 1.2 μmol·L-1 against PC-3 and HL-60 cells respectively, which is worth further study.