title: Novel flavaglines displaying improved cytotoxicity.
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.
authors.affiliation: Therapeutic Innovation Laboratory (UMR 7200), Department of Medicinal Chemistry, Faculté de Pharmacie, CNRS-Université de Strasbourg, Illkirch, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Thuaud
authors.forename: Nigel
authors.initials: N
authors.lastname: Ribeiro
authors.forename: Christian
authors.initials: C
authors.lastname: Gaiddon
authors.forename: Thierry
authors.initials: T
authors.lastname: Cresteil
authors.forename: Laurent
authors.initials: L
authors.lastname: Désaubry
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans