In vitro biological activities of a series of 2 beta-substituted analogues of 1 alpha,25-dihydroxyvitamin D3.

Abstract

Biological activities of a series of 2beta-substituted analogues of 1alpha,25-dihydroxyvitamin D3 [1alpha,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 regulation of the hydroxyalkyl and hydroxyalkoxy 2beta-substituted analogues were almost comparable to those of 1alpha,25(OH)2D3, while the alkyl and alkenyl analogues were much less active than 1alpha,25(OH)2D3. This study investigated the biological evaluation of a series of 2beta-substituted analogues at the molecular level, with regard to the structural differences of alkyl, alkenyl, hydroxyalkyl, hydroxyalkoxy, alkoxy, hydroxy and chloro substituents at the 2beta-position of 1alpha,25(OH)2D3.

• Authors: N Tsugawa, K Nakagawa, M Kurobe, Y Ono, N Kubodera, K Ozono, T Okano
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 23 Issue 1 Pg. 66-71 (Jan 2000) ISSN: 0918-6158 [Print] Japan
• PMID: 10706413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Calcitriol
• Vitamin D-Binding Protein
• dihydroxy-vitamin D3
• Vitamin D
• Cholecalciferol
• Cytochrome P-450 Enzyme System
• Steroid Hydroxylases
• Vitamin D3 24-Hydroxylase

Topics

• Animals
• Binding, Competitive
• Cattle
• Cell Division (drug effects)
• Cholecalciferol (analogs & derivatives, metabolism)
• Cytochrome P-450 Enzyme System (genetics)
• HL-60 Cells
• Humans
• Kinetics
• Protein Binding
• Rats
• Receptors, Calcitriol (metabolism)
• Steroid Hydroxylases (genetics)
• Structure-Activity Relationship
• Transcriptional Activation (drug effects)
• Transfection
• Vitamin D (analogs & derivatives, metabolism, pharmacology)
• Vitamin D-Binding Protein (blood, metabolism)
• Vitamin D3 24-Hydroxylase