文章基本信息

标题：Biological Activity Profiles of 1α, 25-Dihydroxyvitamin D2, D3, D4, D7, and 24-Epi-1α, 25-dihydroxyvitamin D2
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作者：Naoko TSUGAWA ; Kimie NAKAGAWA ; Yuko KAWAMOTO 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：1999
卷号：22
期号：4
页码：371-377
DOI：10.1248/bpb.22.371
出版社：The Pharmaceutical Society of Japan
摘要：We have synthesized several 1α, 25-dihydroxyvitamin D [1α, 25(OH)₂D] derivatives and evaluated their biological activity in terms of their binding affinity for the vitamin D receptor (VDR) and vitamin D-binding protein(DBP), antiproliferative ro differentiation-inducing effects on human promyelocytic leukemic HL-60 cells, and transcriptional activity on a rat 25-hydroxyvitamin D₃-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), and human osteocalcin gene promoter, including a VDRE in transfected human osteosarcoma MG-63 cells. Furthermore, human VDR- or retinoic acid X receptor α (RXRα)-mediated luciferase activities of the derivatives were also measured by a one-hybrid system in human epitheloid carcinoma, cervix HeLa cells and African green monkey kidney CV-1 cells. Binding affinity for VDR, bone-resorbing activity, antiproliferative and cell-differentiating effects, transactivation potencies on target genes and VDR- or RXRα-mediated gene regulations of 1α, 25(OH)₂D₂ and 1α, 25(OH)₂D₄ were almost comparable to the effects of 1α, 25(OH)₂D₃ while 24-epi-1α, 25(OH)₂D₂ and 1α, 25(OH)₂D₇ were much less active than 1α, 25(OH)₂D₃ in these respects. This is the first report concerning biological assessment of 1α, 25(OH)₂D₂, 1α, 25(OH)₂D₃, 1α, 25(OH)₂D₄, 24-epi-1α, 25(OH)₂D₂ and 1α, 25(OH)₂D₇ at the molecular level, especially with regards to the structural differences at the 24R- or 24S-methyl group and a double bond between carbons 22 and 23 in the side chain of 1α, 25(OH)₂D derivatives.
关键词：1α, 25-dihydroxyvitamin D derivative;receptor binding;cell proliferation;cell differentiation;transactivation;bone resorption