Synthesis of 2α- and 2β-(3-hydroxypropyl)-7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 and their biological activity

被引：2

作者：

Sawada, Daisuke ^{[1
,3
]}

Ochiai, Eiji ^{[2
]}

Takeuchi, Akiko ^{[2
]}

Kakuda, Shinji ^{[2
]}

Kamimura-Takimoto, Midori ^{[2
]}

Kawagoe, Fumihiro ^{[1
]}

Kittaka, Atsushi ^{[1
]}

机构：

[1] Teikyo Univ, Fac Pharmaceut Sci, Itabashi Ku, 2-11-1 Kaga, Tokyo 1738605, Japan

[2] Teijin Pharma Ltd, Teijin Inst Biomed Res, 4-3-2 Hino, Tokyo 1918512, Japan

[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2017年 / 173卷

基金：

日本学术振兴会;

关键词：

Synthesis; 7,8-cis-19-norvitamin D-3 analog; Vitamin D receptor; VDR binding affinity; Transactivation; BINDING CONFIGURATION; DERIVATIVES; CANCER;

D O I：

10.1016/j.jsbmb.2016.09.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

According to the binding mode of 14-epi-1 alpha,25-dihydroxy-19-nortachysterol in the ligand binding domain of human vitamin D receptor (hVDR), i.e., 5,6- and 7,8-s-trans configuration that was shown by X-ray co-crystallographic analysis, 7,8-cis-locked 1 alpha,25(OH)(2)D-3 analogs were synthesized. In this paper, the synthesis and biological activity of 2 alpha- and 2 beta-(3-hydroxypropyl)-7,8-cis-14-epi-1 alpha,25-dihydroxy-19-norvitamin D-3 are reported. The A-ring and CD-ring precursors for the Julia-Kociensky coupling reaction to create a diene system of the target molecules were prepared using our original methods. hVDR binding affinity and osteocalcin promoter transactivation activity of the new 7,8-cis-14-epi-vitamin D-3 analogs were evaluated. Interestingly, the 2 beta-substituted 7,8-cis-analog was a better binder for hVDR than the 2 alpha-isomeric counterpart. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：79 / 82

页数：4

共 8 条

[1]

Holick MF., 2011, Vitamin D, V1, P13, DOI [10.1016/b978-0-12-381978-9.10002-2, DOI 10.1016/B978-0-12-381978-9.10002-2]

[2]

Kittaka A, 2009, ANTICANCER RES, V29, P3563

[3] 19-Norvitamin D analogs for breast cancer therapy [J].