Synthesis, estrogenic activity, and anti-osteoporosis effects in ovariectomized rats of resveratrol oligomer derivatives

  • Eur J Med Chem. 2015 Sep 18:102:26-38. doi: 10.1016/j.ejmech.2015.07.042.
Xiao-Dong Hao  1 ,  Jun Chang  1 ,  Bo-Yin Qin  2 ,  Chen Zhong  1 ,  Zhi-Bo Chu  1 ,  Jin Huang  3 ,  Wen-Jiang Zhou  4 ,  Xun Sun  5
Affiliations
  • 1. Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
  • 2. Shanghai Public Health Clinical Center, 2901 Caolang Road, Shanghai 201508, China.
  • 3. School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
  • 4. Shanghai Public Health Clinical Center, 2901 Caolang Road, Shanghai 201508, China. Electronic address: [email protected].
  • 5. Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, 221 West Yanan Road, Shanghai 200040, China. Electronic address: [email protected].
PMID: 26241875 DOI: 10.1016/j.ejmech.2015.07.042
Abstract

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 ERβ 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 μg/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 μg/kg. Therefore, isopaucifloral F may be a promising lead compound for the treatment of postmenopausal osteoporosis.

Keywords
Bone mineral density; Estrogen receptor; Isopaucifloral F; Micro-CT; Osteoporosis.
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