In vitro biological activities of a series of 2β-substituted analogues of 1α, 25-dihydroxyvitamin D3

N Tsugawa, K Nakagawa, M Kurobe, Y ONO… - Biological and …, 2000 - jstage.jst.go.jp
N Tsugawa, K Nakagawa, M Kurobe, Y ONO, N KUBODERA, K OZONO, T OKANO
Biological and Pharmaceutical Bulletin, 2000jstage.jst.go.jp
抄録 Biological activities of a series of 2β-substituted analogues of 1α, 25-dihydroxyvitamin
D 3 [1α, 25 (OH) 2 D 3] 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 D
3-24-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 …
抄録
Biological activities of a series of 2β-substituted analogues of 1α, 25-dihydroxyvitamin D 3 [1α, 25 (OH) 2 D 3] 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 D 3-24-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) 2 D 3, while the alkyl and alkenyl analogues were much les active than 1α, 25 (OH) 2 D 3. 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) 2 D 3.
jstage.jst.go.jp