Synthesis and structure-activity relationships of radicicol derivatives and WNT-5A expression inhibitory activity.
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.
Shinonaga
Hideki
H
Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co, Ltd, Saitama-shi, Saitama, Japan. h.shinonaga@po.rd.taisho.co.jp
Noguchi
Toshiya
T
Ikeda
Akiko
A
Aoki
Mari
M
Fujimoto
Natsuko
N
Kawashima
Akira
A
D020405:Dermis / Q000166:cytology / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D008958:Models, Molecular; D015394:Molecular Structure; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D013329:Structure-Activity Relationship; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000071818:Wnt-5a Protein
D018942:Macrolides; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C035359:monorden