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

共 33 条

[21] In vivo evidence for a novel pathway of vitamin D3 metabolism initiated by P450scc and modified by CYP27B1 [J].

Slominski, Andrzej T. ;

Kim, Tae-Kang ;

Shehabi, Haleem Z. ;

Semak, Igor ;

Tang, Edith K. Y. ;

Nguyen, Minh N. ;

Benson, Heather A. E. ;

Korik, Elena ;

Janjetovic, Zorica ;

Chen, Jianjun ;

Yates, Charles R. ;

Postlethwaite, Arnold ;

Li, Wei ;

Tuckey, Robert C. .

FASEB JOURNAL, 2012, 26 (09) :3901-3915

[22] Products of Vitamin D3 or 7-Dehydrocholesterol Metabolism by Cytochrome P450scc Show Anti-Leukemia Effects, Having Low or Absent Calcemic Activity [J].

Slominski, Andrzej T. ;

Janjetovic, Zorica ;

Fuller, Brian E. ;

Zmijewski, Michal A. ;

Tuckey, Robert C. ;

Nguyen, Minh N. ;

Sweatman, Trevor ;

Li, Wei ;

Zjawiony, Jordan ;

Miller, Duane ;

Chen, Tai C. ;

Lozanski, Gerard ;

Holick, Michael F. .

PLOS ONE, 2010, 5 (03)

[23] Hydroxylation of CYP11A1-Derived Products of Vitamin D3 Metabolism by Human and Mouse CYP27B1 [J].

Tang, Edith K. Y. ;

Chen, Jianjun ;

Janjetovic, Zorica ;

Tieu, Elaine W. ;

Slominski, Andrzej T. ;

Li, Wei ;

Tuckey, Robert C. .

DRUG METABOLISM AND DISPOSITION, 2013, 41 (05) :1112-1124

[24] Purified Mouse CYP27B1 Can Hydroxylate 20,23-Dihydroxyvitamin D3, Producing 1α,20,23-Trihydroxyvitamin D3, Which Has Altered Biological Activity [J].

Tang, Edith K. Y. ;

Li, Wei ;

Janjetovic, Zorica ;

Nguyen, Minh N. ;

Wang, Zhao ;

Slominski, Andrzej ;

Tuckey, Robert C. .

DRUG METABOLISM AND DISPOSITION, 2010, 38 (09) :1553-1559

[25]

Thill M, 2015, ANTICANCER RES, V35, P1189

[26] Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1 [J].

Tieu, Elaine W. ;

Li, Wei ;

Chen, Jianjun ;

Kim, Tae-Kang ;

Ma, Dejian ;

Slominski, Andrzej T. ;

Tuckey, Robert C. .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2015, 149 :153-165

[27] Rat CYP24A1 acts on 20-hydroxyvitamin D3 producing hydroxylated products with increased biological activity [J].

Tieu, Elaine W. ;

Tang, Edith K. Y. ;

Chen, Jianjun ;

Li, Wei ;

Nguyen, Minh N. ;

Janjetovic, Zorica ;

Slominski, Andrzej ;

Tuckey, Robert C. .

BIOCHEMICAL PHARMACOLOGY, 2012, 84 (12) :1696-1704

[28] Kinetics of vitamin D3 metabolism by cytochrome P450scc (CYP11A1) in phospholipid vesicles and cyclodextrin [J].

Tuckey, Robert C. ;

Nguyen, Minh N. ;

Slominski, Andrzej .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (11) :2619-2626

[29] Production of 22-Hydroxy Metabolites of Vitamin D3 by Cytochrome P450scc (CYP11A1) and Analysis of Their Biological Activities on Skin Cells [J].

Tuckey, Robert C. ;

Li, Wei ;

Shehabi, Haleem Z. ;

Janjetovic, Zorica ;

Nguyen, Minh N. ;

Kim, Tae-Kang ;

Chen, Jianjun ;

Howell, Danielle E. ;

Benson, Heather A. E. ;

Sweatman, Trevor ;

Baldisseri, Donna M. ;

Slominski, Andrzej .

DRUG METABOLISM AND DISPOSITION, 2011, 39 (09) :1577-1588

[30] Metabolism of 1α-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1α,20-dihydroxyvitamin D3 [J].

Tuckey, Robert C. ;

Janjetovic, Zorica ;

Li, Wei ;

Nguyen, Minh N. ;

Zmijewski, Michal A. ;

Zjawiony, Jordan ;

Slominski, Andrzej .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2008, 112 (4-5) :213-219

← 1 2 3 4 →