title: Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-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 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.
authors.forename: Zongtao
authors.initials: Z
authors.lastname: Lin
authors.forename: Srinivasa Reddy
authors.initials: SR
authors.lastname: Marepally
authors.forename: Dejian
authors.initials: D
authors.lastname: Ma
authors.forename: Linda K
authors.initials: LK
authors.lastname: Myers
authors.affiliation: Department of Veterans Affairs Medical Center, Memphis, Tennessee 38104, United States.
authors.forename: Arnold E
authors.initials: AE
authors.lastname: Postlethwaite
authors.affiliation: School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA 6009, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Tuckey
authors.affiliation: School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA 6009, Australia.
authors.forename: Chloe Y S
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Tae-Kang
authors.initials: TK
authors.lastname: Kim
authors.forename: Junming
authors.initials: J
authors.lastname: Yue
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.|VA Medical Center at Birmingham, Birmingham, Alabama 35294, United States.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
authors.forename: Duane D
authors.initials: DD
authors.lastname: Miller
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D006900:Hydroxylation; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018167:Receptors, Calcitriol; D011971:Receptors, Immunologic; C118756:dihydroxy-vitamin D3; C108073:leukocyte-associated immunoglobulin-like receptor 1; D014807:Vitamin D; D007371:Interferon-gamma; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase