Synthesis and Biological Activities of 1α,4α,25- and 1α,4β,25-Trihydroxyvitamin D3 and Their Metabolism by Human CYP24A1 and UDP-Glucuronosyltransferase

Daisuke Sawada; Yuya Tsukuda; Kaori Yasuda; Toshiyuki Sakaki; Hiroshi Saito; Ken-ichiro Takagi; Kazuya Takenouchi; Tai C. Chen; G. Satyanarayana Reddy; Atsushi Kittaka

doi:10.1248/cpb.c12-00526

Notes

Synthesis and Biological Activities of 1α,4α,25- and 1α,4β,25-Trihydroxyvitamin D₃ and Their Metabolism by Human CYP24A1 and UDP-Glucuronosyltransferase

Daisuke Sawada, Yuya Tsukuda, Kaori Yasuda, Toshiyuki Sakaki, Hiroshi Saito, Ken-ichiro Takagi, Kazuya Takenouchi, Tai C. Chen, G. Satyanarayana Reddy, Atsushi Kittaka

Author information

Daisuke Sawada
Faculty of Pharmaceutical Sciences, Teikyo University
Yuya Tsukuda
Faculty of Pharmaceutical Sciences, Teikyo University
Kaori Yasuda
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University
Toshiyuki Sakaki
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University
Hiroshi Saito
Teijin Institute for Bio-medical Research, Teijin Pharma Ltd.
Ken-ichiro Takagi
Teijin Institute for Bio-medical Research, Teijin Pharma Ltd.
Kazuya Takenouchi
Teijin Institute for Bio-medical Research, Teijin Pharma Ltd.
Tai C. Chen
Section of Endocrinology, Diabetes and Nutrition, School of Medicine, Boston University
G. Satyanarayana Reddy
Epimer LLC
Department of Chemistry, Brown University
Atsushi Kittaka
Faculty of Pharmaceutical Sciences, Teikyo University

Keywords: trihydroxyvitamin D₃, vitamin D receptor, metabolism, human CYP24A1, human liver microsome, UDP-glucuronosyltransferase

JOURNAL FREE ACCESS

2012 Volume 60 Issue 10 Pages 1343-1346

DOI https://doi.org/10.1248/cpb.c12-00526

Details

Abstract

A previous report has demonstrated the existence of a C4-hydroxylated vitamin D₂ metabolite in serum of rats treated with pharmacological doses of vitamin D₂. However, the biological significance and metabolic fate of this metabolite have not been described. To explore its potential biological activities, we therefore synthesized 1α,4α,25-trihydroxyvitamin D₃ and its diastereoisomer, 1α,4β,25-trihydroxyvitamin D₃, using Trost Pd-mediated coupling reaction, and studied their vitamin D receptor (VDR) binding affinity, osteocalcin promoter transactivation activity, and their further metabolism by human CYP24A1 as well as by human liver microsomal fraction based on CYP- and UDP-glucuronosyltransferases (UGTs)-reactions.

Corresponding author

Register with J-STAGE for free!