Novel flavaglines displaying improved cytotoxicity

  • J Med Chem. 2011 Jan 13;54(1):411-5. doi: 10.1021/jm101318b.
Frédéric Thuaud  1 ,  Nigel Ribeiro ,  Christian Gaiddon ,  Thierry Cresteil ,  Laurent Désaubry
Affiliations
  • 1. Therapeutic Innovation Laboratory (UMR 7200), Department of Medicinal Chemistry, Faculté de Pharmacie, CNRS-Université de Strasbourg, Illkirch, France.
PMID: 21142180 DOI: 10.1021/jm101318b
Abstract

Novel flavagline analogues were synthesized and examined with respect to their cytotoxicity. Structural features critical to the potential of this class of Anticancer natural products were unraveled. We demonstrated, in particular, that the introduction of substituants at C-2 has a deleterious effect on multidrug resistance. Replacement of the hydroxy at C-1 by an aminoformyl with the opposite configuration enhances the cytotoxicity and led to a compound that reduces tumors growth in an allograft model at nontoxic doses.