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

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 journal › Article

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 language	English
Pages (from-to)	1343-1346
Number of pages	4
Journal	Chemical and Pharmaceutical Bulletin
Volume	60
Issue number	10
DOIs	https://doi.org/10.1248/cpb.c12-00526
Publication status	Published - Oct 1 2012
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Chemistry(all)
Drug Discovery

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Sawada, D., Tsukuda, Y., Yasuda, K., Sakaki, T., Saito, H., Takagi, K. I., Takenouchi, K., Chen, T. C., Reddy, G. S., & Kittaka, A. (2012). Synthesis and biological activities of 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D₃ and their metabolism by human CYP24A1 and UDP-glucuronosyltransferase. Chemical and Pharmaceutical Bulletin, 60(10), 1343-1346. https://doi.org/10.1248/cpb.c12-00526

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, 01.10.2012, p. 1343-1346.

Research output: Contribution to journal › Article

Sawada, D, Tsukuda, Y, Yasuda, K, Sakaki, T, Saito, H, Takagi, KI, Takenouchi, K, Chen, TC, Reddy, GS & Kittaka, A 2012, 'Synthesis and biological activities of 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D₃ and their metabolism by human CYP24A1 and UDP-glucuronosyltransferase', Chemical and Pharmaceutical Bulletin, vol. 60, no. 10, pp. 1343-1346. https://doi.org/10.1248/cpb.c12-00526

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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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.",

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AU - Sakaki, Toshiyuki

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AU - Takagi, Ken Ichiro

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