College of Pharmacy, Catholic University of Daegu, Hayang, 712-702, Korea.
Molecules. 2010 Jun 21;15(6):4408-22. doi: 10.3390/molecules15064408.
2-Chloro-, 2-bromo- and 2-azido-1,4,6-androstatriene-3,17-diones were synthesized from 1alpha,2alpha-epoxy-4,6-androstadiene-3,17-dione (2) using HCl, HBr and NaN(3), respectively. Compound 2 was also reacted with NaCN to give 2-cyano-1,4,6-androstatriene-3,17-dione (5) and 2beta-cyano-1alpha-hydroxy-4,6-androstadiene-3,17-dione (6). 6Alpha,7alpha-epoxy-1,4-androstadiene-3,17-dione (8) was reacted with HCl, HBr and NaN(3) to form the corresponding 7beta-chloro-, 7beta-bromo- and 7beta-azido-6alpha-hydroxy-1,4-androstadiene-3,17-diones. The cytotoxic activity of these compounds towards T47D (estrogen-dependent) and MDA-MB231 (estrogen-independent) breast cancer cell lines was evaluated. The 6alpha-hydroxy-7beta-substituted analogs were more active than the 2-substituted analogs on both cell lines. Compound 2 showed the highest selective activity against the T47D (IC(50) 7.1 microM) cell line and 5 showed good cytotoxic activity on MDA-MB231 (IC(50) 18.5 microM) cell line, respectively. The 6alpha,7alpha-epoxy analog 8 also showed high cytotoxic activity on both cell lines (IC(50) 17.3 microM on T47D and IC(50) 26.9 microM on MDA-MB231).
2-氯-、2-溴-和 2-叠氮-1α，2α-环氧-4，6-雄甾二烯-3，17-二酮分别由 1α，2α-环氧-4，6-雄甾二烯-3，17-二酮（2）与 HCl、HBr 和 NaN3 反应制得。化合物 2 还与 NaCN 反应生成 2-氰基-1α，4，6-雄甾二烯-3，17-二酮（5）和 2β-氰基-1α-羟基-4，6-雄甾二烯-3，17-二酮（6）。6α，7α-环氧-1α，4-雄甾二烯-3，17-二酮（8）与 HCl、HBr 和 NaN3 反应生成相应的 7β-氯代、7β-溴代和 7β-叠氮代-6α-羟基-1α，4-雄甾二烯-3，17-二酮。评估了这些化合物对 T47D（雌激素依赖性）和 MDA-MB231（雌激素非依赖性）乳腺癌细胞系的细胞毒性活性。6α-羟基-7β-取代类似物在两种细胞系上均比 2-取代类似物更具活性。化合物 2 对 T47D（IC50 为 7.1μM）细胞系表现出最高的选择性活性，而 5 对 MDA-MB231（IC50 为 18.5μM）细胞系具有良好的细胞毒性活性。6α，7α-环氧类似物 8 对两种细胞系也表现出高细胞毒性活性（对 T47D 的 IC50 为 17.3μM，对 MDA-MB231 的 IC50 为 26.9μM）。
