Synthesis and anti-osteoporotic evaluation of certain 3-amino-2-hydroxypropoxyisoflavone derivatives.
We report herein the synthesis and anti-osteoporotic evaluation of certain 3-amino-2-hydroxypropoxyisoflavone derivatives. The results indicated that 3-(3,4-dimethoxyphenyl)-7-(oxiran-2-ylmethoxy)-4H-chromen-4-one (4) and 3-{4-[3-(cyclohexylamino)-2-hydroxypropoxy]phenyl}-7-methoxy-4H-chromen-4-one (5a) exhibited significant inhibitory effects on osteoclast activity (TRAP activity in RAW 264.7 with an ED(50) of 0.56 and 2.28 microM respectively). Both compounds have also exhibited very strong osteogenic effects, approximately a 10-fold effect of Ipriflavone on mineralization of osteoblasts (MC3T3E1 cells, a preosteoblast cell line derived from calvaria of C57BL/6 mice). Results indicated the potency on enhancing mineralization in D1 cells (a bone marrow mesenchymal cell line derived from BALB/c mice) decreased in an order 4>Ipriflavone>5a. However, the potency on enhancing mineralization in human adipose tissue derived stem cells (hADSCs) decreased in an order 5a>4>Raloxifene>Ipriflavone. Compound 5a has been found to be non-cytotoxic and especially active in the enhancement of mineralization in human adipose tissue derived stem cells. Therefore, 5a was selected as a potential lead for further structural optimization.
Tseng
Chih-Hua
CH
Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
Chen
Yeh-Long
YL
Lu
Chih-Ming
CM
Wang
Chih-Kuang
CK
Tsai
Yin-Tung
YT
Lin
Ru-Wei
RW
Chen
Chain-Fu
CF
Chang
Yu-Fang
YF
Wang
Gwo-Jaw
GJ
Ho
Mei-Ling
ML
Tzeng
Cherng-Chyi
CC