2-Chloro-, 2-bromo- and 2-azido-1,4,6-androstatriene-3,17-diones were synthesized from 1α,2α-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 2β-cyano-1α-hydroxy-4,6-androstadiene-3,17-dione (
6). 6α,7α-Epoxy-1,4-androstadiene-3,17-dione (
8) was reacted
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2-Chloro-, 2-bromo- and 2-azido-1,4,6-androstatriene-3,17-diones were synthesized from 1α,2α-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 2β-cyano-1α-hydroxy-4,6-androstadiene-3,17-dione (
6). 6α,7α-Epoxy-1,4-androstadiene-3,17-dione (
8) was reacted with HCl, HBr and NaN
3 to form the corresponding 7β-chloro-, 7β-bromo- and 7β-azido-6α-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 6α-hydroxy-7β-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 μM) cell line and
5 showed good cytotoxic activity on MDA-MB231 (IC
50 18.5 μM) cell line, respectively. The 6α,7α-epoxy analog
8 also showed high cytotoxic activity on both cell lines (IC
50 17.3 μM on T47D and IC
50 26.9 μM on MDA-MB231).
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