Synthesis and chloroquine-enhancing activity of Na-deacetyl-ferrocenoyl-strychnobrasiline

Lydie Pélinski (1) , Dorothée Razafimahefa (2) , Marie-Thérèse Martin (3) , David Ramanitrahasimbola (4) , Philippe Rasoanaivo (4) , Jacques S. Brocard (1)

1 UCCS - Unité de Catalyse et Chimie du Solide - UMR 8181
2 Laboratoire de Chimie Appliquée aux Substances Naturelles
3 ICSN - Institut de Chimie des Substances Naturelles
4 Laboratoire de Pharmacognosie Appliquée aux Maladies Infectieuses

Several strychnobrasiline derivatives have been synthesized to overcome the lack of in vivo reversal activity of the parent compound. In the present study, Na-deacetyl-ferrocenoyl-strychnobrasiline was synthesized by condensing Na-deacetyl-strychnobrasiline with ferrocenic acid previously treated with oxalyl chloride. While the in vitro antiplasmodial activity of the test compound (IC50 = 4.83 lg/mL) was increased 15-fold compared to that of strychnobrasiline, and the in vitro enhancing activity was found to be similar to that of the parent compound, the compound was devoid of any in vivo potentiating effect, and an antagonistic effect was even observed at higher doses. Based on the overall results on the hemisynthesis of strychnobrasiline derivatives for better reversal activity, this strategy has appeared to be of little value for useful drugs.

Mots clés: Chemosensitizing activity; Strychnobrasiline; Na-deacetyl-ferrocenoyl strychnobrasiline; Chemosensitizing activity.

Domaines: Chimie thérapeutique

Lydie Pélinski, Dorothée Razafimahefa, Marie-Thérèse Martin, David Ramanitrahasimbola, Philippe Rasoanaivo, et al.. Synthesis and chloroquine-enhancing activity of Na-deacetyl-ferrocenoyl-strychnobrasiline. Bioorganic and Medicinal Chemistry Letters, 2005, 15, pp.1239-1241. ⟨10.1016/j.bmcl.2004.11.067⟩. ⟨hal-00115540⟩