新型D-断和D-高雄甾烷衍生物的合成及其抗肿瘤活性
Synthesis and antitumor activity of new D-seco and D-homo androstane derivatives.
作者信息
Djurendić Evgenija A, Zavis Marina P, Sakac Marija N, Canadi Janos J, Kojić Vesna V, Bogdanović Gordana M, Penov Gasi Katarina M
机构信息
Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
出版信息
Steroids. 2009 Nov;74(12):983-8. doi: 10.1016/j.steroids.2009.07.007. Epub 2009 Jul 29.
Starting from 3beta-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4-9 were synthesized. On the other hand, 3beta-hydroxy-17-oxa-D-homoandrost-5-ene-16-one (10) yielded the new d-homo derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, prostate cancer AR-, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC(50) values being 2 microM and 0.55 microM, respectively. Compounds 6 (10 microM) and 14 (9 microM) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1-3, 5-8, 10 and 12-15 were not toxic to normal fetal lung fibroblasts cells, MRC-5.
以3β-羟基-17-氧代-16,17-断雄甾-5-烯-16-腈（1）为起始原料，合成了新型16,17-断雄甾烷衍生物4 - 9。另一方面，3β-羟基-17-氧杂-D-高雄甾-5-烯-16-酮（10）生成了新型D-高衍生物12、13和15。评估了所选化合物对三种肿瘤细胞系（人乳腺腺癌ER +，MCF-7；人乳腺腺癌ER -，MDA-MB-231；前列腺癌AR -，PC-3；以及正常胎儿肺成纤维细胞，MRC-5）的体外抗增殖活性。化合物3和12对PC-3细胞显示出较强的抗增殖活性，IC(50)值分别为2 microM和0.55 microM。化合物6（10 microM）和14（9 microM）对MDA-MB-231细胞显示出中等活性。合成的化合物1 - 3、5 - 8、10和12 - 15对正常胎儿肺成纤维细胞MRC-5无毒。
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