Chemical Synthesis and Biological Activities of 205,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives

被引：24

作者：

Lin, Zongtao ^{[1
]}

Marepally, Srinivasa Reddy ^{[1
]}

Ma, Dejian ^{[1
]}

Myers, Linda K. ^{[2
]}

Postlethwaite, Arnold E. ^{[2
,4
]}

Tuckey, Robert C. ^{[5
]}

Cheng, Chloe Y. S. ^{[5
]}

Kim, Tae-Kang ^{[6
]}

Yue, Junming ^{[3
]}

Slominski, Andrzej T. ^{[6
,7
]}

Miller, Duane D. ^{[1
]}

Li, Wei ^{[1
]}

机构：

[1] Univ Tennessee, Hlth Sci Ctr, Dept Pharmaceut Sci, Memphis, TN 38163 USA

[2] Univ Tennessee, Hlth Sci Ctr, Med Div Connect Tissue Dis, Memphis, TN 38163 USA

[3] Univ Tennessee, Hlth Sci Ctr, Pathol & Lab Med, Memphis, TN 38163 USA

[4] Dept Vet Affairs Med Ctr, Memphis, TN 38104 USA

[5] Univ Western Australia, Sch Chem & Biochem, Crawley, WA 6009, Australia

[6] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA

[7] VA Med Ctr Birmingham, Birmingham, AL 35294 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 19期

关键词：

CYTOCHROME P450SCC CYP11A1; VITAMIN-D-RECEPTOR; CANCER-CELL-LINES; KAPPA-B ACTIVITY; 20-HYDROXYVITAMIN D3; IN-VIVO; ANTIPROLIFERATIVE ACTIVITY; 20,23-DIHYDROXYVITAMIN D3; INHIBITS PROLIFERATION; HUMAN KERATINOCYTES;

D O I：

10.1021/acs.jmedchem.5b00881

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Bioactive vitamin D3 metabolites 20S,24S-dihydroxyvitamin D3 [20S,24S(OH)(2)D3] and 20S,24R-dihydroxyvitamin D3 [20S,24R(OH)(2)D-3] 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 alpha-hydroxylation by CYP27B1 were determined. Their corresponding la-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 alpha,20S,24R(OH)(2)D-3 being the most potent compound.

引用

页码：7881 / 7887

页数：7

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