期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 136, 期 -, 页码 3-8出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2013.02.004
关键词
Vitamin D-3; Vitamin D receptor; Vitamin D analogs; Transactivation; Human osteosarcoma cell; Ovariectomized (OVX) rat model
资金
- Grants-in-Aid for Scientific Research [24590021] Funding Source: KAKEN
Up to the present, numerous vitamin D derivatives have been synthesized, but most of them have straight side chains, and there are few publications described about in vitro and in vivo evaluations on bone by vitamin D derivatives. In our previous paper, we reported the synthesis of various C-2 substituted vitamin D derivatives (2b-2i) with a 2,2-dimethylcyclopentanone unit in the CD-ring side chains, and that the derivatives have strong activity for enhancing bone growth. On the basis of results, this time, we report the synthesis of 2 alpha-substituted vitamin D-3 derivatives with chiral cyclopentanone (3-6 and 12-16). These derivatives were obtained by Pd-coupling reaction with A-ring precursor and CD-rings precursor. We evaluated novel derivatives in vitro assays, for affinities for VDR and transactivation assays by human osteosarcoma (HOS) cells. In this research, we demonstrated that some novel vitamin D derivatives (12-MP, 13-MP, 15-MP and 16-LP) have strong transactivation activities in spite of lower affinity for VDR than 1. In addition, we also demonstrated that these derivatives have strong activities for enhancing bone growth using OVX therapeutic rats. This article is part of a Special Issue entitled 'Vitamin D Workshop'. (c) 2013 Elsevier Ltd. All rights reserved.
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