First synthesis of separable isomeric testosterone dimers showing differential activities on prostate cancer cells

被引：21

作者：

Bastien, Dominic ^{[1
]}

Leblanc, Valerie ^{[1
]}

Asselin, Eric ^{[1
]}

Berube, Gervais ^{[1
]}

机构：

[1] Univ Quebec, Dept Chim Biol, Grp Rech Oncol & Endocrinol Mol, Trois Rivieres, PQ G9A 5H7, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 07期

关键词：

Testosterone; Dimers; Androgen receptor; Prostate cancer; ANDROGEN RECEPTOR; BINDING-AFFINITY; DERIVATIVES; METATHESIS;

D O I：

10.1016/j.bmcl.2010.02.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis of two separable isomeric testosterone dimers is reported. The dimers are made from testosterone in a 5 step sequence and with 36% overall yield. The key dimerization step was performed using Hoveyda-Grubb's metathesis catalysts on 7 alpha-allyltestosterone with 75% yield. The synthesis led to separable isomeric dimers (trans and cis, 2:1). X-ray diffraction crystallography, performed on monocrystal of the minor isomer, confirms the cis geometry of the double bound between the two testosterone units. MTT assays showed that the cis dimer has the highest activity against prostate cancer cell lines. The novel cis dimer is more active than the antiandrogen cyproterone acetate indicating the possible therapeutic value of this molecule. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2078 / 2081

页数：4

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