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 | |
| Publication status | Published - Oct 2012 |
| Externally published | Yes |
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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 journal › Article
}
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 -