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

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

SUBMITTER: Lin Z

PROVIDER: S-EPMC4613797 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Lin Zongtao Z Marepally Srinivasa Reddy SR Ma Dejian D Myers Linda K LK Postlethwaite Arnold E AE Tuckey Robert C RC Cheng Chloe Y S CY Kim Tae-Kang TK Yue Junming J Slominski Andrzej T AT Miller Duane D DD Li Wei W

Journal of medicinal chemistry 20150928 19

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 respe ...[more]

PMID: 26367019

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