Zhou Wu-Xi, Sun Yuan-Yuan, Yuan Wei-Hui, Zhao Yu-Qing
Department of Traditional Chinese Medicine Chemical, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Department of Traditional Chinese Medicine Chemical, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Steroids. 2017 May;121:32-39. doi: 10.1016/j.steroids.2017.03.005. Epub 2017 Mar 18.
(20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH-PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH-PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH-PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH-PPD and its derivatives was tested and the results showed that the solubility of 25-OCH-PPD sulfamic acid and diacid derivatives were better than that of 25-OCH-PPD in water, which may provide valuable data for the research and development of new anti-tumor agents.
（20R）-25-甲氧基-达玛烷-3β，12β，20-三醇（25-OCH-PPD，AD-1）是一种具有抗肿瘤潜力的达玛烷型皂苷元。为了寻找比我们之前鉴定的化合物25-OCH-PPD效力更高的新型抗肿瘤药物，设计并合成了11种新型磺酸和二酸衍生物，它们可以提高水溶性，并有助于获得良好的药效和药代动力学特征。通过标准MTT法检测了它们在MCF-7、A-549、HCT-116和BGC-823细胞系以及一种正常细胞系中的体外抗肿瘤活性。结果表明，与化合物25-OCH-PPD相比，化合物1、4和5在几乎所有细胞系中均表现出更高的细胞毒性活性，同时对正常细胞的毒性较低。特别是，化合物1在体外试验中表现出最佳的抗肿瘤活性。测试了25-OCH-PPD及其衍生物的水溶性，结果表明25-OCH-PPD磺酸和二酸衍生物在水中的溶解度优于25-OCH-PPD，这可能为新型抗肿瘤药物的研发提供有价值的数据。
