Chinese Journal of Organic Chemistry >
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).
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
Li Longxiang , Xie Longyong , Wang Fengjun , He Weimin , Xiang Jiannan . Synthesis and Antitumor Activity of 17-(2',5'-Disubstituted-oxazolyl)-androsta-4,16-dien-3-one[J]. Chinese Journal of Organic Chemistry, 2014 , 34(9) : 1864 -1869 . DOI: 10.6023/cjoc201402032
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