文章基本信息

标题：In Vitro Biological Activities of a Series of 2β-Substituted Analogues of 1α, 25-Dihydroxyvitamin D3
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作者：Naoko TSUGAWA ; Kimie NAKAGAWA ; Mayuko KUROBE 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2000
卷号：23
期号：1
页码：66-71
DOI：10.1248/bpb.23.66
出版社：The Pharmaceutical Society of Japan
摘要：Biological activities of a series of 2β-substituted analogues of 1α, 25-dihydroxyvitamin D₃ [1α, 25(OH)₂D₃] were evaluated in vitro in terms of their binding affinity with regard to calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP). Additionally, reporter gene luciferase activities using either a rat 25-hydroxyvitamin D₃-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), in transfected rat osteoblast-like ROS17/2.8 cells, or a human VDR-GAL4 modified two-hybrid system in transfected human epitheloid carcinoma, cervix HeLa cells were examined. Binding affinity for VDR, transactivation potency on the target gene and VDR-mediated gene ergulation of the hydroxyalkyl and hydroxyalkoxy 2β-substituted analogues were almost comparable to those of 1α, 25(OH)₂D₃, while the alkyl and alkenyl analogues were much les active than 1α, 25(OH)₂D₃. This study investigated the biological evaluation of a series of 2β-substituted analogues at the molecular level, with regard to the structural differences of alkyl, alkenyl, hydroxyalkyl, hydroxyalkoxy, alkoxy, hydroxy and chloro substituents at the 2β-position of 1α, 25(OH)₂D₃.
关键词：1α, 25-dihydroxyvitamin D3;2β-analogue;receptor binding;cell differentiation;gene transactivation