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

Zongtao Lin, Srinivasa Reddy Marepally, Dejian Ma, Linda Myers, Arnold Postlethwaite, Robert C. Tuckey, Chloe Y.S. Cheng, Tae Kang Kim, Junming Yue, Andrzej T. Slominski, Duane Miller, Wei Li

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 1α-hydroxylation by CYP27B1 were determined. Their corresponding 1α-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 1α,20S,24R(OH)2D3 being the most potent compound.

Original languageEnglish (US)
Pages (from-to)7881-7887
Number of pages7
JournalJournal of Medicinal Chemistry
Volume58
Issue number19
DOIs
StatePublished - Oct 8 2015

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Hydroxyl Radical
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Calcitriol Receptors
Cholecalciferol
Hydroxylation
Anti-Inflammatory Agents
dihydroxy-vitamin D3

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives. / Lin, Zongtao; Marepally, Srinivasa Reddy; Ma, Dejian; Myers, Linda; Postlethwaite, Arnold; Tuckey, Robert C.; Cheng, Chloe Y.S.; Kim, Tae Kang; Yue, Junming; Slominski, Andrzej T.; Miller, Duane; Li, Wei.

In: Journal of Medicinal Chemistry, Vol. 58, No. 19, 08.10.2015, p. 7881-7887.

Research output: Contribution to journalArticle

Lin, Zongtao ; Marepally, Srinivasa Reddy ; Ma, Dejian ; Myers, Linda ; Postlethwaite, Arnold ; Tuckey, Robert C. ; Cheng, Chloe Y.S. ; Kim, Tae Kang ; Yue, Junming ; Slominski, Andrzej T. ; Miller, Duane ; Li, Wei. / Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives. In: Journal of Medicinal Chemistry. 2015 ; Vol. 58, No. 19. pp. 7881-7887.
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abstract = "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 1α-hydroxylation by CYP27B1 were determined. Their corresponding 1α-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 1α,20S,24R(OH)2D3 being the most potent compound.",
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AU - Ma, Dejian

AU - Myers, Linda

AU - Postlethwaite, Arnold

AU - Tuckey, Robert C.

AU - Cheng, Chloe Y.S.

AU - Kim, Tae Kang

AU - Yue, Junming

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AU - Li, Wei

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