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

作　　者：董远 马养民[1] 马思悦 孙任伟 DONG Yuan;MA Yangmin;MA Siyue;SUN Renwei(Key Laboratory of Chemical Additives for China National Light Industry,College of Chemistry and Chemical Engineering.Shaanxi University of Science&Technology,Xi’an 710021,China)

机构地区：[1]中国轻工业轻化工助剂重点实验室,陕西科技大学化学与化工学院,西安710021

出　　处：《高等学校化学学报》2024年第4期54-61,共8页Chemical Journal of Chinese Universities

基　　金：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);中国博士后科学基金(批准号:2022M711994)资助。

摘　　要：利用N-甲基吲哚对类固醇药物的前驱体16-脱氢孕烯醇酮乙酸酯(16-DPA)的D环C16位进行修饰,采用ZrCl_4-乙酸乙酯廉价催化体系,合成了16个3β-乙酰氧基-16α-3'-吲哚孕烯醇酮化合物和6个3β-羟基-16α-3'-吲哚孕烯醇酮衍生物.该方法具有收率高、立体选择性好和底物适应性强等优点.通过噻唑蓝(MTT)比色法测试了22个化合物对三阴性乳腺癌细胞(MDA-MB-231)的抗肿瘤活性.初步测试结果表明, 3β-乙酰氧基-16α-3'-吲哚孕烯醇酮化合物6h和6i对MDA-MB-231癌细胞有较好的抑制活性,其半数抑制浓度(IC_(50))分别为18.07和23.22μmol/L;而化合物7a~7f均对MDA-MB-231癌细胞有较好的抑制活性,其中化合物7e的抗肿瘤活性最好,其IC_(50)为12.50μmol/L.目标化合物为药物筛选提供了一定的参考.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(IC_(50))of 18.07 and 23.22μmol/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 IC_(50) 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 

分 类 号：O629.23[理学—有机化学]