Xiao Shengnan, Chen Shuai, Sun Yuanyuan, Zhou Wuxi, Piao Huri, Zhao Yuqing
Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, China.
Shenyang Pharmaceutical University, Shenyang 110016, China.
Bioorg Med Chem Lett. 2017 Sep 1;27(17):4204-4211. doi: 10.1016/j.bmcl.2017.06.061. Epub 2017 Jun 24.
In the current work, 13 novel panaxadiol (PD) derivatives were synthesized by reacting with chloroacetyl chloride and bromoacetyl bromide. Their in vitro antitumor activities were evaluated on three human tumor cell lines (HCT-116, BGC-823, SW-480) and three normal cells (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2) by MTT assay. Compared with PD, the results demonstrated that compound 1e, 2d, 2e showed significant anti-tumor activity against three tumor cell lines, the IC50 value of compound 2d against HCT-116 was the lowest (3.836μM). The anti-tumor activity of open-ring compounds are significantly better than the compounds of C-25 cyclization. Compound 1f, 2f, 2g showed the strong anti-tumor activity. The IC50 value of compound 2g against BGC-823 and SW-480 were the lowest (0.6μM and 0.1μM, respectively). Combined with cytotoxicity test, the IC50 value of compound 1e, 2d, 2e are greater than 100. the open-ring compounds (1f, 2f, 2g) showed a strong toxicity. The toxicity of 1f is lower than 2f and 2g. These compounds may be useful for the development of novel antiproliferative agents.
在当前工作中，通过与氯乙酰氯和溴乙酰溴反应合成了13种新型人参二醇（PD）衍生物。通过MTT法在三种人类肿瘤细胞系（HCT-116、BGC-823、SW-480）和三种正常细胞（人胃上皮细胞系-GES-1、毛囊真皮乳头细胞系-HHDPC和大鼠心肌细胞系-H9C2）上评估了它们的体外抗肿瘤活性。与PD相比，结果表明化合物1e、2d、2e对三种肿瘤细胞系显示出显著的抗肿瘤活性，化合物2d对HCT-116的IC50值最低（3.836μM）。开环化合物的抗肿瘤活性明显优于C-25环化的化合物。化合物1f、2f、2g显示出较强的抗肿瘤活性。化合物2g对BGC-823和SW-480的IC50值最低（分别为0.6μM和0.1μM）。结合细胞毒性试验，化合物1e、2d、2e的IC50值大于100，开环化合物（1f、2f、2g）显示出较强的毒性。1f的毒性低于2f和2g。这些化合物可能有助于开发新型抗增殖剂。
