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 › peer-review

9 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 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

Access to Document

10.1248/cpb.c12-00526

Cite this

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, 10.2012, p. 1343-1346.

Research output: Contribution to journal › Article › peer-review

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.

@article{7db2fd34d0884153a90f6fce3dcd5ee8,

title = "Synthesis and biological activities of 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D3 and their metabolism by human CYP24A1 and UDP-glucuronosyltransferase",

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.",

keywords = "Human CYP24A1, Human liver microsome, Metabolism, Trihydroxyvitamin D, UDP-glucuronosyltransferase, Vitamin D receptor",

author = "Daisuke Sawada and Yuya Tsukuda and Kaori Yasuda and Toshiyuki Sakaki and Hiroshi Saito and Takagi, {Ken Ichiro} and Kazuya Takenouchi and Chen, {Tai C.} and Reddy, {G. Satyanarayana} and Atsushi Kittaka",

year = "2012",

month = oct,

doi = "10.1248/cpb.c12-00526",

language = "English",

volume = "60",

pages = "1343--1346",

journal = "Chemical and Pharmaceutical Bulletin",

issn = "0009-2363",

publisher = "Pharmaceutical Society of Japan",

number = "10",

}

TY - JOUR

T1 - Synthesis and biological activities of 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D3 and their metabolism by human CYP24A1 and UDP-glucuronosyltransferase

AU - Sawada, Daisuke

AU - Tsukuda, Yuya

AU - Yasuda, Kaori

AU - Sakaki, Toshiyuki

AU - Saito, Hiroshi

AU - Takagi, Ken Ichiro

AU - Takenouchi, Kazuya

AU - Chen, Tai C.

AU - Reddy, G. Satyanarayana

AU - Kittaka, Atsushi

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - Human CYP24A1

KW - Human liver microsome

KW - Metabolism

KW - Trihydroxyvitamin D

KW - UDP-glucuronosyltransferase

KW - Vitamin D receptor

UR - http://www.scopus.com/inward/record.url?scp=84867199841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867199841&partnerID=8YFLogxK

U2 - 10.1248/cpb.c12-00526

DO - 10.1248/cpb.c12-00526

M3 - Article

C2 - 23036975

AN - SCOPUS:84867199841

VL - 60

SP - 1343

EP - 1346

JO - Chemical and Pharmaceutical Bulletin

JF - Chemical and Pharmaceutical Bulletin

SN - 0009-2363

IS - 10

ER -