Planta Med 2008; 74 - PG12
DOI: 10.1055/s-0028-1084765

Novel potential antitumor analogues of fagaronine and nitidine in the Benzo[c]phenanthroline series

C Genès 1, S Prado 2, FH Porée 1, S Michel 1, F Tillequin 1
  • 1Laboratoire de Pharmacognosie, U.M.R./CNRS N° 8638 U. Paris Descartes, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006 Paris, France
  • 2Laboratoire de Chimie et Biochimie des Substances Naturelles, UMR 5154 CNRS/MNHN, Muséum National d'Histoire Naturelle, 57 rue Cuvier, CP54, 75005 Paris

Fagaronine [1] and nitidine [2] are two benzophenanthridine alkaloids naturally occurring in numerous Rutaceae species. Both of them exhibit interesting cytotoxic properties in vitro and anti-leukaemic activities in vivo. Their lack of significant activity against solid tumors led us to study the structure activity relationships [3], with the double aim of increasing their cellular uptake and cytotoxic potency. In this context, we currently develop structural analogues differing from the natural products by the replacement of the benzene A ring by a pyridine and the introduction of a dialkylaminoalkylamino side chain at position 6. These two modifications permit a significant increase of the cytotoxic activity. The mechanism of action of these new compounds at both molecular and cellular levels is under current study.

References: 1. Messmer, WM. (1972)J. Pharm. Sci. 61:1858–9.

2. Arthur, HR. et al. (1958) Chem. Ind. 1514.

3. Prado, S. et al. (2004) Bioorg. Med. Chem. 12:3943–3953.