萝卜素衍生物的合成、构效关系及WNT-5A表达抑制活性

Synthesis and structure-activity relationships of radicicol derivatives and WNT-5A expression inhibitory activity.

作者信息

Shinonaga Hideki, Noguchi Toshiya, Ikeda Akiko, Aoki Mari, Fujimoto Natsuko, Kawashima Akira

机构信息

Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co, Ltd, Saitama-shi, Saitama, Japan.

出版信息

Bioorg Med Chem. 2009 Jul 1;17(13):4622-35. doi: 10.1016/j.bmc.2009.04.060. Epub 2009 May 3.

DOI:10.1016/j.bmc.2009.04.060

PMID:19447629

Abstract

WNT-5A, a secretory glycoprotein, is related to the proliferation of dermal papilla cells. To develop a hair-growth stimulant, we have been searching for inhibitors of WNT-5A expression. We identified radicicol (1) as an active compound, and synthesized several radicicol derivatives. Among them, 6,7-dihydro-10alpha-hydroxy radicicol (31) was found to function as a new potent WNT-5A expression inhibitor with relatively low toxicity and excellent stability.

摘要

WNT-5A是一种分泌性糖蛋白，与毛乳头细胞的增殖有关。为开发一种毛发生长刺激剂，我们一直在寻找WNT-5A表达的抑制剂。我们鉴定出萝卜素（1）为活性化合物，并合成了几种萝卜素衍生物。其中，6,7-二氢-10α-羟基萝卜素（31）被发现是一种新的强效WNT-5A表达抑制剂，具有相对较低的毒性和出色的稳定性。