高等学校化学学报2024，Vol.45Issue(4)：1-8,8.DOI:10.7503/cjcu20230449
基于薯蓣皂苷元催化合成N-甲基吲哚孕烯醇酮化合物及其抗肿瘤活性
Catalytic Synthesis of N-methylindopregnenolone Compounds Based on Diosgenin and Their Anti-tumor Activity
摘要
Abstract
The D-ring C16 position of 16-dehydropregnenolone acetate(16-DPA),a precursor of steroidal drugs,was modified using N-methylindole,and the inexpensive catalytic system of ZrCl4-ethyl acetate was employed to synthesize sixteen(3β-acetyloxy-16α-3'-indolopregnenolone compounds)as well as to synthesize six 3β-hydroxy-16α-3'-indolone pregnenolone derivatives.The method has the advantages of high yield,good stereoselectivity and substrate adaptability.Twenty-two compounds were tested for antitumor activity in triple-negative breast cancer cells(MDA-MB-231)by thiazolyl blue(MTT)assay.The preliminary test results showed that among the 3β-acetoxy-16α-3'-indolopregnenolone compounds,compounds 6h and 6i had better cancer inhibitory activities against MDA-MB-231 cancer cells with median inhibition concentration(IC50)of 18.07 and 23.22 μmol/L,respectively,whereas all of compounds 7a—7f had better cancer inhibitory activities against MDA-MB-231 cancer cells,among which compound 7e showed the best antitumor activity with an IC50 of 12.50 μmol/L.These compounds provide some references for drug screening.关键词
16-脱氢孕烯醇酮乙酸酯/孕烯醇酮/N-甲基吲哚/抗肿瘤活性Key words
16-Dehydropregnenolone acetate/Pregnenolone/N-methylindole/Anti-tumor activity分类
化学化工引用本文复制引用
董远,马养民,马思悦,孙任伟..基于薯蓣皂苷元催化合成N-甲基吲哚孕烯醇酮化合物及其抗肿瘤活性[J].高等学校化学学报,2024,45(4):1-8,8.基金项目
国家自然科学基金(批准号:22178205)、陕西省重点研发计划项目(批准号:2022GY-203)和中国博士后科学基金(批准号:2022M711994)资助. Supported by the National Natural Science Foundation of China(No.22178205),the Key Research and Development Program of Shaanxi Province,China(No.2022GY-203)and the China Postdoctoral Science Foundation(No.2022M711994). （批准号:22178205）
