Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1伪-Hydroxyl Derivatives

详细信息    查看全文

• 作者：Zongtao Lin ; Srinivasa Reddy Marepally ; Dejian Ma ; Linda K. Myers ; Arnold E. Postlethwaite ; Robert C. Tuckey ; Chloe Y. S. Cheng ; Tae-Kang Kim ; Junming Yue ; Andrzej T. Slominski ; Duane D. Miller ; Wei Li
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：October 8, 2015
• 年：2015
• 卷：58
• 期：19
• 页码：7881-7887
• 全文大小：416K
• ISSN：1520-4804

文摘

Bioactive vitamin D3 metabolites 20S,24S-dihydroxyvitamin D3 [20S,24S(OH)₂D3] and 20S,24R-dihydroxyvitamin D3 [20S,24R(OH)₂D3] were chemically synthesized and confirmed to be identical to their enzymatically generated counterparts. The absolute configurations at C24 and its influence on the kinetics of 1伪-hydroxylation by CYP27B1 were determined. Their corresponding 1伪-hydroxyl derivatives were subsequently produced. Biological comparisons of these products showed different properties with respect to vitamin D3 receptor activation, anti-inflammatory activity, and antiproliferative activity, with 1伪,20S,24R(OH)₂D3 being the most potent compound.