Synthesis of 2beta-substituted-14-epi-previtamin D3 and testing of its genomic activity

2beta-substituted analogs of 14-epi-previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The V...

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Bibliographic Details
Published in:The Journal of steroid biochemistry and molecular biology 2010-07, Vol.121 (1-2), p.20-24
Main Authors: Sawada, Daisuke, Tsukuda, Yuya, Saito, Hiroshi, Takagi, Ken-ichiro, Ochiai, Eiji, Ishizuka, Seiichi, Takenouchi, Kazuya, Kittaka, Atsushi
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Chemistry, Pharmaceutical - methods
Cholecalciferol - analogs & derivatives
Cholecalciferol - chemical synthesis
Cholecalciferol - chemistry
Cholecalciferol - pharmacology
Drug Design
Epoxy Compounds - chemistry
Humans
Models, Biological
Models, Chemical
Osteocalcin - genetics
Phosphines - chemistry
Promoter Regions, Genetic
Receptors, Calcitriol - metabolism
Stereoisomerism
Transcriptional Activation
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Summary:2beta-substituted analogs of 14-epi-previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1 nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46 nM, respectively.
ISSN:1879-1220
DOI:10.1016/j.jsbmb.2010.02.035