6-羟基及6-羧基-B-降胆甾醇-3-羧酸酯的合成及其抗肿瘤活性研究  

Synthesis and in vitro antiproliferative activity of 6-hydroxy-B-norcholestrol-3-carboxylates and 6-carboxyl-B-norcholestrol-3-carboxylates

作　　者：李君彦 庞春玲 程扬 黄燕敏 崔建国 庞丽萍 LI Jun-yan;PANG Chun-ling;CHENG Yang;HUANG Yan-ming;CUI Jian-guo;PANG Li-ping(Guangxi Key Laboratory of Natural Polymer Chemistry and Physics,College of Chemistry and Material Science,Nanning Normal University,Nanning 530001,China)

机构地区：[1]广西天然高分子材料与物理重点实验室,南宁师范大学化学与材料科学学院,广西南宁530001

出　　处：《化学研究与应用》2023年第8期1886-1896,共11页Chemical Research and Application

基　　金：国家自然科学基金项目(22267016)资助;广西重点研发计划项目(桂科AB21220015)资助;广西中青年教师科研基础能力提升项目(2023KY0396)资助。

摘　　要：从胆甾醇出发,在3-位引入不同的酯基,随后臭氧氧化开环,进一步缩合环化,最后将环化产物的6-醛基氧化成为羧基或还原成为醇,得到某些6-羟基或6-羧基-B-降胆甾醇-3-羧酸酯衍生物。通过NMR及HRMS等现代分析方法对目标产物进行了结构表征。同时采用人乳腺导管癌细胞(T47D),人卵巢癌细胞(SKOV3),人乳腺癌细胞(MCF-7)对目标化合物进行体外抑制肿瘤细胞增殖活性研究,人肾上皮细胞(HEK293T)作为对照。结果表明B-降胆甾醇3-羧酸酯的6-醛基被氧化成为羧酸后,得到的产物比其前体及6-醛基还原成为羟基的产物具有更好的抑制肿瘤细胞增殖活性,而且这些化合物对HEK293T细胞没有表现出明显的细胞毒性。本研究的结果为甾体化合物作为抗肿瘤药物的研究开发提供了有益的参考。Beginning with cholesterol,various ester groups were introduced to the 3-position,followed by ring-opening of ozone oxidation and further condensation cyclization,and some B-norcholestrol-3-carboxylates were yielded.Finally,the 6-aldehyde group of the B-norcholestrol-3-carboxylates was either oxidized to a carboxyl group or reduced to an alcohol,resulting in the production of 6-carboxy or 6-hydroxyl-B-norcholesterol-3-carboxylate derivatives.Modern analytical methods such as NMR and HRMS were used to structurally characterize the target products.An in vitro anti-proliferation assay was conducted to evaluate the activity of the target compounds on human breast ductal carcinoma cells(T47D),human ovarian cancer cells(SKOV3),and human breast cancer cells(MCF-7).Human renal epithelial cells(HEK293T)were used as the control.The results showed that oxidation of the 6-aldehyde of B-norcholesterol-3-carboxylates to carboxyl yielded products with better inhibitory activity on tumor cell proliferation than the precursor and the products of 6-aldehyde reduced to hydroxyl group.Additionally,these compounds exhibited no significant cytotoxicity to HEK293T cells.This study provided valuable insight into the research and development of steroidal compounds as antitumor drugs.

关 键 词：胆甾醇 B-降胆甾醇 6-羟基-B-降胆固醇-3-羧酸酯 6-羧基-B-降胆固醇-3-羧酸酯 抗肿瘤活性 

分 类 号：O629.29[理学—有机化学]