Synthesis, estrogenic activity, and anti-osteoporosis effects in ovariectomized rats of resveratrol oligomer derivatives
Synthesis, estrogenic activity, and anti-osteoporosis effects in ovariectomized rats of resveratrol oligomer derivatives
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白藜芦醇低聚物衍生物的合成、雌激素活性和对去势大鼠的抗骨质疏松作用
DOI：
10.1016/j.ejmech.2015.07.042
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发表时间：
2015-09-18
影响因子：
6.7
通讯作者：
Sun, Xun
中科院分区：
文献类型：
--
作者：
Hao, Xiao-Dong;Chang, Jun;Sun, Xun
合成了三个系列的白藜芦醇低聚物衍生物，包括吲哚类、吲烯类和八氢戊二烯类衍生物，其中有10个为新化合物。通过酵母双杂交实验，确定化合物2、14F和4d为ERβ激动剂，并进一步选择化合物2(异叶花F)进行体内抗骨质疏松活性评价。与假手术组和阳性对照组相比，异黄花F(10mug/kg)对去卵巢(OVX)雌性大鼠具有显著的抗骨质疏松作用，其指标包括：骨密度、骨体积/组织体积、骨小梁厚度、骨小梁间距/间距和血清生化指标。异落叶松的LD_(50)>5 mg/kg，有效剂量(ED)约为10微克/公斤。因此，异黄花F有希望成为治疗绝经后骨质疏松症的先导化合物。(C)2015年爱思唯尔·马森公司。版权所有。
Three series of resveratrol oligomer derivatives were synthesized, including the indenone-type, indene-type and octahydropentalene-type derivatives, among which ten derivatives were novel compounds. Compounds 2, 14f, and 4d were confirmed as ER beta agonists by yeast two-hybrid assay, and compound 2 (isopaucifloral F) was further chosen to evaluate its anti-osteoporosis activity in vivo. Compared with the sham-operated and the positive control groups, isopaucifloral F (10 mu g/kg) showed a notable anti-osteoporosis effect in the ovariectomized (OVX) female rats based on a micro-CT analysis and the following measurements: bone mineral density, bone volume/tissue volume, trabecular thickness, trabecular separation/spacing, and the serum biochemical parameters. LD50 of isopaucifloral F was found to be greater than 5 mg/kg and its effective dose (ED) was found to be about 10 mu g/kg. Therefore, isopaucifloral F may be a promising lead compound for the treatment of postmenopausal osteoporosis. (C) 2015 Elsevier Masson SAS. All rights reserved.