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

Autor:	Ken Ichiro Takagi, Kazuya Takenouchi, Toshiyuki Sakaki, Kaori Yasuda, Daisuke Sawada, Tai C. Chen, Yuya Tsukuda, Hiroshi Saito, G. Satyanarayana Reddy, Atsushi Kittaka
Rok vydání:	2012
Předmět:	Chemistry Metabolite Vitamin D3 24-Hydroxylase General Chemistry General Medicine Metabolism Calcitriol receptor chemistry.chemical_compound Transactivation Biochemistry CYP24A1 Drug Discovery Vitamin D and neurology Receptor
Zdroj:	Chemical and Pharmaceutical Bulletin. 60:1343-1346
ISSN:	1347-5223 0009-2363
Popis:	A previous report has demonstrated the existence of a C4-hydroxylated vitamin D(2) metabolite in serum of rats treated with pharmacological doses of vitamin D(2). 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 D(3) and its diastereoisomer, 1α,4β,25-trihydroxyvitamin D(3), 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::5407b1d78b51f718a74f9479d42c2182 https://doi.org/10.1248/cpb.c12-00526 Zobrazit plný text záznamu