Synthesis and anti-osteoporotic evaluation of certain 3-amino-2-hydroxypropoxyisoflavone derivatives
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- 作者：Chih-Hua Tseng ; Yeh-Long Chen ; Chih-Ming Lu ; Chih-Kuang Wang ; Yin-Tung Tsai ; Ru-Wei Lin ; Chain-Fu Chen ; Yu-Fang Chang ; Gwo-Jaw Wang ; Mei-Ling Ho ; Cherng-Chyi Tzeng
- 关键词：Isoflavone ; 3-Amino-2-hydroxypropoxyisoflavone ; Anti-osteoporotic activity
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2009
- 出版时间：September 2009
- 年：2009
- 卷：44
- 期：9
- 页码：3621-3626
- 全文大小：373 K
文摘
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 ED50 of 0.56 and 2.28 μM 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.