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

Z. Lin, S.R. Marepally, D. Ma, L.K. Myers, A.E. Postlethwaite, Robert Tuckey, Chloe Cheng, T.K. Kim, J. Yue, A.T. Slominski, D.D. Miller, W. Li

Research output: Contribution to journalArticle

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Abstract

© 2015 American Chemical Society. 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
Pages (from-to)7881-7887
JournalJournal of Medicinal Chemistry
Volume58
Issue number19
DOIs
Publication statusPublished - 2015

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

Cite this

Lin, Z. ; Marepally, S.R. ; Ma, D. ; Myers, L.K. ; Postlethwaite, A.E. ; Tuckey, Robert ; Cheng, Chloe ; Kim, T.K. ; Yue, J. ; Slominski, A.T. ; Miller, D.D. ; Li, W. / 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 = "{\circledC} 2015 American Chemical Society. 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.",
author = "Z. Lin and S.R. Marepally and D. Ma and L.K. Myers and A.E. Postlethwaite and Robert Tuckey and Chloe Cheng and T.K. Kim and J. Yue and A.T. Slominski and D.D. Miller and W. Li",
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Lin, Z, Marepally, SR, Ma, D, Myers, LK, Postlethwaite, AE, Tuckey, R, Cheng, C, Kim, TK, Yue, J, Slominski, AT, Miller, DD & Li, W 2015, 'Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives' Journal of Medicinal Chemistry, vol. 58, no. 19, pp. 7881-7887. https://doi.org/10.1021/acs.jmedchem.5b00881

Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives. / Lin, Z.; Marepally, S.R.; Ma, D.; Myers, L.K.; Postlethwaite, A.E.; Tuckey, Robert; Cheng, Chloe; Kim, T.K.; Yue, J.; Slominski, A.T.; Miller, D.D.; Li, W.

In: Journal of Medicinal Chemistry, Vol. 58, No. 19, 2015, p. 7881-7887.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives

AU - Lin, Z.

AU - Marepally, S.R.

AU - Ma, D.

AU - Myers, L.K.

AU - Postlethwaite, A.E.

AU - Tuckey, Robert

AU - Cheng, Chloe

AU - Kim, T.K.

AU - Yue, J.

AU - Slominski, A.T.

AU - Miller, D.D.

AU - Li, W.

PY - 2015

Y1 - 2015

N2 - © 2015 American Chemical Society. 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.

AB - © 2015 American Chemical Society. 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.

U2 - 10.1021/acs.jmedchem.5b00881

DO - 10.1021/acs.jmedchem.5b00881

M3 - Article

VL - 58

SP - 7881

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

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