Synthesis of 2- and 7- Substituted C19 Steroids Having a 1,4,6-Triene or 1,4-Diene Structure and Their Cytotoxic Effects on T47D and MDA-MB231 Breast Cancer Cells

Molecules

Minwoo Kim¹ 

[1] College of Pharmacy, Catholic University of Daegu, Hayang, 712-702, Korea

关键词: breast cancer;    T47D cell;    MDA-MB231 cell;    2-substituted 1;    4;    6-androstatriene-3;    17-dione;    6α-hydroxy-7β-substituted-1;    4-androstadiene-3;    17-dione;   

DOI  :  10.3390/molecules15064408

来源: mdpi

【 摘 要 】

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 NaN₃, 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 NaN₃ 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 (IC₅₀ 7.1 μM) cell line and 5 showed good cytotoxic activity on MDA-MB231 (IC₅₀ 18.5 μM) cell line, respectively. The 6α,7α-epoxy analog 8 also showed high cytotoxic activity on both cell lines (IC₅₀ 17.3 μM on T47D and IC₅₀ 26.9 μM on MDA-MB231).

【 授权许可】

CC BY   
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