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20S,24S/R-二羟基维生素D3差向异构体及其1α-羟基衍生物的化学合成与生物活性

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

作者信息

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

机构信息

Department of Veterans Affairs Medical Center, Memphis, Tennessee 38104, United States.

School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA 6009, Australia.

出版信息

J Med Chem. 2015 Oct 8;58(19):7881-7. doi: 10.1021/acs.jmedchem.5b00881. Epub 2015 Sep 28.

DOI:10.1021/acs.jmedchem.5b00881
PMID:26367019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4613797/
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.

摘要

生物活性维生素D3代谢物20S,24S-二羟基维生素D3 [20S,24S(OH)2D3]和20S,24R-二羟基维生素D3 [20S,24R(OH)2D3]经化学合成，并被证实与酶促生成的对应物相同。确定了C24处的绝对构型及其对CYP27B1进行1α-羟基化动力学的影响。随后制备了它们相应的1α-羟基衍生物。这些产物的生物学比较显示，在维生素D3受体激活、抗炎活性和抗增殖活性方面具有不同特性，其中1α,20S,24R(OH)2D3是最有效的化合物。

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