| Literature DB >> 35168121 |
Pawel Brzeminski1, Adrian Fabisiak1, Radomir M Slominski2, Tae-Kang Kim3, Zorica Janjetovic3, Ewa Podgorska3, Yuwei Song2, Mohammad Saleem3, Sivani B Reddy3, Shariq Qayyum3, Yuhua Song4, Robert C Tuckey5, Venkatram Atigadda3, Anton M Jetten6, Rafal R Sicinski7, Chander Raman3, Andrzej T Slominski8.
Abstract
New and more efficient routes of chemical synthesis of vitamin D3 (D3) hydroxy (OH) metabolites, including 20S(OH)D3, 20S,23S(OH)2D3 and 20S,25(OH)2D3, that are endogenously produced in the human body by CYP11A1, and of 20S,23R(OH)2D3 were established. The biological evaluation showed that these compounds exhibited similar properties to each other regarding inhibition of cell proliferation and induction of cell differentiation but with subtle and quantitative differences. They showed both overlapping and differential effects on T-cell immune activity. They also showed similar interactions with nuclear receptors with all secosteroids activating vitamin D, liver X, retinoic acid orphan and aryl hydrocarbon receptors in functional assays and also as indicated by molecular modeling. They functioned as substrates for CYP27B1 with enzymatic activity being the highest towards 20S,25(OH)2D3 and the lowest towards 20S(OH)D3. In conclusion, defining new routes for large scale synthesis of endogenously produced D3-hydroxy derivatives by pathways initiated by CYP11A1 opens an exciting era to analyze their common and differential activities in vivo, particularly on the immune system and inflammatory diseases.Entities:
Keywords: Active forms of vitamin D; Biological activity; Keratinocytes; Receptors for vitamin D; Vitamin D
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Year: 2022 PMID： 35168121 PMCID： PMC8923993 DOI： 10.1016/j.bioorg.2022.105660
Source DB: PubMed Journal: Bioorg Chem ISSN： 0045-2068 Impact factor: 5.275