Synthesis and anti-osteoporotic evaluation of certain 3-amino-2-hydroxypropoxyisoflavone derivatives

被引：16

作者：

Tseng, Chih-Hua ^{[2
]}

Chen, Yeh-Long ^{[2
]}

Lu, Chih-Ming ^{[2
]}

Wang, Chih-Kuang ^{[2
]}

Tsai, Yin-Tung ^{[2
]}

Lin, Ru-Wei ^{[1
]}

Chen, Chain-Fu ^{[1
]}

Chang, Yu-Fang ^{[1
]}

Wang, Gwo-Jaw ^{[1
,3
]}

Ho, Mei-Ling ^{[1
,4
]}

Tzeng, Cherng-Chyi ^{[2
]}

机构：

[1] Kaohsiung Med Univ, Orthopaed Res Ctr, Kaohsiung 807, Taiwan

[2] Kaohsiung Med Univ, Coll Life Sci, Fac Med & Appl Chem, Kaohsiung 807, Taiwan

[3] Kaohsiung Med Univ, Sch Med, Dept Orthopaed, Kaohsiung 807, Taiwan

[4] Kaohsiung Med Univ, Sch Med, Dept Physiol, Kaohsiung 807, Taiwan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 09期

关键词：

Isoflavone; 3-Amino-2-hydroxypropoxyisoflavone; Anti-osteoporotic activity; OSTEOCLAST DIFFERENTIATION; POSTMENOPAUSAL WOMEN; ISOFLAVONE DERIVATIVES; BONE LOSS; IN-VIVO; GENISTEIN; RALOXIFENE; AGENTS; APOPTOSIS; CELLS;

D O I：

10.1016/j.ejmech.2009.02.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M 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 > Sa. However, the potency on enhancing mineralization in human adipose tissue derived stem cells (hADSCs) decreased in an order Sa > 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, Sa was selected as a potential lead for further structural optimization. (C) 2009 Published by Elsevier Masson SAS.

引用

页码：3621 / 3626

页数：6

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