17-(2',5'-二取代噁唑基)-雄甾-4,16-二烯-3-酮的合成及抗肿瘤活性研究
收稿日期: 2014-02-27
修回日期: 2014-04-15
网络出版日期: 2014-05-05
基金资助
国家自然科学基金(Nos. 21302048, 21276068)、中国博士后科学基金(No. 2013M540625)、湖南省自然科学基金(No. 11JJ5008)资助项目.
Synthesis and Antitumor Activity of 17-(2',5'-Disubstituted-oxazolyl)-androsta-4,16-dien-3-one
Received date: 2014-02-27
Revised date: 2014-04-15
Online published: 2014-05-05
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21302048, 21276068), the China Postdoctoral Science Foundation (No. 2013M540625) and the Natural Science Foundation of Hunnan Province (No. 11JJ5008).
以4-雄烯二酮1为原料，用金催化甾炔法设计并合成了一系列17-(2'，5'-二取代噁唑基)-雄甾-4，16-二烯-3-酮衍生物4a～4k. 所合成产物通过1H NMR，13C NMR，IR和 HRMS方法进行了结构表征. 以阿比特龙为阳性对照，通过3-(4，5-二甲基噻唑-2)-2，5-二苯基四氮唑溴盐(MTT)法测试了目标化合物对MCF-7(人乳腺癌细胞)、A549(人肺癌细胞)、Bel-7402(人肝癌细胞)、Hela(人宫颈癌细胞)和PC-3M-1E8(人前列腺癌细胞)的体外抗肿瘤活性. 结果表明大多数化合物表现出了较好的抗肿瘤活性，其中化合物4c，4g，4i 和4j 的抗肿瘤活性与阳性对照物阿比特龙相当，且所测化合物对MCF-7有较好选择性作用，其IC50值在3.0～25.5 μmol/L 之间.
黎龙香 , 谢龙勇 , 王风君 , 何卫民 , 向建南 . 17-(2',5'-二取代噁唑基)-雄甾-4,16-二烯-3-酮的合成及抗肿瘤活性研究[J]. 有机化学, 2014 , 34(9) : 1864 -1869 . DOI: 10.6023/cjoc201402032
A series of 17-(2',5'-disubstituted-oxazolyl)-androsta-4,16-dien-3-one derivatives 4a～4k were designed and synthesized via the gold-catalyzed steroidal alkyne oxidation from 4-androstene-3,17-dione 1. The structures of the targeted compounds were characterized by 1H NMR, 13C NMR, IR and HRMS. These synthesized compounds were screened for in vitro antitumor activity by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against MCF-7 (human breast cancer cell line), A549 (human lung cancer cell line), Bel-7402 (human liver cancer cell line), Hela (human cervical cancer cell line) and PC-3M-1E8 (human prostate cancer cell line) using abiraterone as the positive control. The results revealed that most of compounds showed moderate to significant activity. In particular, compounds 4c, 4g, 4i and 4j exhibited similar antitumor activities compared with that of abiraterone, and all tested compounds displayed higher selectivity against MCF-7 cell line (IC50=3.0～25.5 μmol/L).
Key words： steroids; oxazole; gold-catalyzed; synthesis; antitumor activity
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