In vitro biological activities of a series of 2β-substituted analogues of 1α, 25-dihydroxyvitamin D3
In vitro biological activities of a series of 2β-substituted analogues of 1α, 25-dihydroxyvitamin D3
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1α, 25-二羟基维生素 D3 的一系列 2β 取代类似物的体外生物活性
DOI：
10.1248/bpb.23.66
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发表时间：
2000
影响因子：
2
通讯作者：
T. Okano
中科院分区：
文献类型：
--
作者：
N. Tsugawa;K. Nakagawa;M. Kurobe;Y. Ono;N. Kubodera;K. Ozono;T. Okano
用小牛胸腺胞浆维生素D受体（VDR）和大鼠血浆维生素D结合蛋白（DBP）与1α，25-二羟维生素D3 [1α，25（OH）2D 3] 2β取代类似物的结合亲和力，评价了它们的体外生物活性。此外，在转染的大鼠成骨细胞样ROS 17/2.8细胞中使用大鼠25-羟基维生素D3-24-羟化酶基因启动子（包括两个维生素D反应元件（VDRE））或在转染的人上皮样癌宫颈HeLa细胞中使用人VDR-GAL 4修饰的双杂交系统，检测报告基因荧光素酶活性。羟烷基和羟烷氧基2β-取代类似物对VDR的结合亲和力、对靶基因的反式激活效力和VDR介导的基因促作用几乎与1α，25（OH）2D 3相当，而烷基和烯基类似物的活性远低于1α，25（OH）2D 3。本研究从分子水平上研究了一系列2β-取代类似物的生物学评价，包括1α，25（OH）2D 3的2β-位烷基、烯基、羟烷基、羟烷氧基、烷氧基、羟基和氯取代基的结构差异。
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.