title: Synthesis and preliminary biological evaluation of new antiproliferative aromatic analogues of 1α,25-dihydroxyvitamin D3.
abstract: In an effort to develop novel vitamin D3 analogues, a series of aromatic compounds was synthetized, using efficient Negishi cross coupling between alkenylzinc reagents of the C,D-ring moiety of vitamin D3, and various substituted aromatic halides as A-ring mimics. The study aimed at exploring the influence of the replacement of the original vitamin D3 diene by a styrene unit on the biological activities. Potency in the induction of the differentiation of HL-60 cells for the lead compound 36 was 12 fold less important than calcitriol correlating with a weaker binding affinity for VDR.
authors.affiliation: Laboratoire de Chimie Thérapeutique, BioCIS-CNRS (UMR 8076), Université Paris-Sud, Faculté de Pharmacie, Rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Thomas
authors.affiliation: Laboratoire de Chimie Thérapeutique, BioCIS-CNRS (UMR 8076), Université Paris-Sud, Faculté de Pharmacie, Rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Brion
authors.affiliation: Laboratoire de Chimie Thérapeutique, BioCIS-CNRS (UMR 8076), Université Paris-Sud, Faculté de Pharmacie, Rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France. Electronic address: jean-francois.peyrat@u-psud.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Peyrat
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C118756:dihydroxy-vitamin D3; D014807:Vitamin D
keywords: Antiproliferative activity; Aromatic analogues of vitamin D3; Negishi coupling reaction