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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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,4 α,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.

Original languageEnglish
Pages (from-to)1343-1346
Number of pages4
JournalChemical and Pharmaceutical Bulletin
Volume60
Issue number10
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

Fingerprint

Ergocalciferols
Glucuronosyltransferase
Metabolites
Bioactivity
Metabolism
Calcitriol Receptors
Osteocalcin
Liver
Transcriptional Activation
Rats
Pharmacology
Serum
Vitamin D3 24-Hydroxylase

Keywords

  • Human CYP24A1
  • Human liver microsome
  • Metabolism
  • Trihydroxyvitamin D
  • UDP-glucuronosyltransferase
  • Vitamin D receptor

ASJC Scopus subject areas

  • Drug Discovery
  • Chemistry(all)

Cite this

Synthesis and biological activities of 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D3 and their metabolism by human CYP24A1 and UDP-glucuronosyltransferase. / Sawada, Daisuke; Tsukuda, Yuya; Yasuda, Kaori; Sakaki, Toshiyuki; Saito, Hiroshi; Takagi, Ken Ichiro; Takenouchi, Kazuya; Chen, Tai C.; Reddy, G. Satyanarayana; Kittaka, Atsushi.

In: Chemical and Pharmaceutical Bulletin, Vol. 60, No. 10, 10.2012, p. 1343-1346.

Research output: Contribution to journalArticle

Sawada, Daisuke ; Tsukuda, Yuya ; Yasuda, Kaori ; Sakaki, Toshiyuki ; Saito, Hiroshi ; Takagi, Ken Ichiro ; Takenouchi, Kazuya ; Chen, Tai C. ; Reddy, G. Satyanarayana ; Kittaka, Atsushi. / Synthesis and biological activities of 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D3 and their metabolism by human CYP24A1 and UDP-glucuronosyltransferase. In: Chemical and Pharmaceutical Bulletin. 2012 ; Vol. 60, No. 10. pp. 1343-1346.
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AU - Takagi, Ken Ichiro

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