Synthesis and preliminary biological evaluation of new antiproliferative aromatic analogues of 1α,25-dihydroxyvitamin D3

  • Eur J Med Chem. 2014 Oct 30:86:381-93. doi: 10.1016/j.ejmech.2014.07.037.
Emmanuel Thomas  1 ,  Jean-Daniel Brion  1 ,  Jean-François Peyrat  2
Affiliations
  • 1. Laboratoire de Chimie Thérapeutique, BioCIS-CNRS (UMR 8076), Université Paris-Sud, Faculté de Pharmacie, Rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France.
  • 2. 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: [email protected].
PMID: 25180926 DOI: 10.1016/j.ejmech.2014.07.037
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.

Keywords
Antiproliferative activity; Aromatic analogues of vitamin D3; Negishi coupling reaction.