苯并咪唑基取代的甾体衍生物合成及其抗肿瘤活性  

Synthesis and Antiproliferative Activity of Some Novel Steroidal Derivatives Containning Benzimidazole Groups

作　　者：甘春芳[1] 刘晓兰[1] 盛海兵 展军颜[1] 吴玉兰 黄燕敏[1] 杨坤 崔建国[1] GAN Chun-fang;LIU Xiao-lan;SHENG Hai-bing;ZHAN Jun-yan;WU Yu-lan;HUANG Yan-min;YANG Kun;CUI Jian-guo(Key Laboratory of Beibu Gulf Environment Change and Resources Utilization,College of Chemistry and Material Science,Guangxi Teachers Education University,Nanning 530001,Guangxi,China;Guangxi Wande Pharmaceutical Co.,Ltd.,Nanning 530105,Guangxi,China)

机构地区：[1]广西师范学院北部湾环境演变与资源利用教育部重点实验室,化学与材料科学学院,广西南宁530001 [2]广西万德药业有限公司,广西南宁530105

出　　处：《精细化工》2018年第12期2078-2086,共9页Fine Chemicals

基　　金：国家自然科学基金项目(21762008、21562007、21462009);广西高校科学技术研究项目(KY2015ZD077);广西南宁市科技专项资助项目(20171125-5)~~

摘　　要：以孕烯醇酮为原料,通过对孕烯醇酮的C-17’支链进行化学修饰,设计合成了18个甾核的C-17’支链为苯并咪唑基取代的甾体化合物。通过IR、1HNMR、13CNMR和HRMS对化合物进行了结构表征,采用溴化噻唑蓝四氮唑(MTT)法测试了这些化合物对人口腔上皮癌细胞(KB)、宫颈癌细胞(HeLa)、人肝癌细胞(HepG)、人鼻咽癌细胞(CNE-2)、乳腺癌细胞(BT474)、卵巢癌细胞(SKOV3)的体外抑制活性。结果表明,部分化合物具有中等程度的活性,其中氟基取代的苯并咪唑甾体化合物5c和6c对人体卵巢癌细胞(SKOV3)具有良好的选择性抑制作用,IC50(半抑制浓度)分别为(15.44±3.8)和(9.2±0.6)μmol/L。该类化合物可为设计开发新型抗肿瘤药物提供参考。Eighteen steroidal derivatives containing benzimidazole heterocycle were designed and synthesized by suitable modification at C17'side chain of pregnenolone.Their structures were characterized by IR,1HNMR,13CNMR and HRMS.The antiproliferative activity of the target compounds in vitro was evaluated against human oral epithelial carcinoma cells (KB),cervical carcinoma (HeLa),liver cancer (HepG),human nasopharyngeal carcinoma (CNE-2),breast cancer (BT474)and ovarian cancer (SKOV3) cells by MTT method.The results showed that some compounds possessed distinct antiproliferative activity against the tested cells.Among these active compounds,compounds 5c and 6c exhibited better selective activity against SKOV3 cells with IC50 values of (15.44±3.8)pmol/L and (9.2±0.6)μmol/L,respectively.The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.

关 键 词：苯并咪唑 甾体化合物 孕烯醇酮 抗肿瘤活性 细胞毒性 医药与日化原料 

分 类 号：O626[理学—有机化学] O629.2[理学—化学]