Synthesis and chloroquine-enhancing activity of Na-deacetyl-ferrocenoyl-strychnobrasiline.
Several strychnobrasiline derivatives have been synthesized to overcome the lack of in vivo reversal activity of the parent compound. In the present study, N(a)-deacetyl-ferrocenoyl-strychnobrasiline was synthesized by condensing N(a)-deacetyl-strychnobrasiline with ferrocenic acid previously treated with oxalyl chloride. While the in vitro antiplasmodial activity of the test compound (IC(50)=4.83 microg/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.
Razafimahefa
Dorothée
D
Laboratoire de Chimie Appliquées aux Substances Naturelles, Faculté des Sciences d'Antananarivo, BP 906, 101-Antananarivo, Madagascar.
Pélinski
Lydie
L
Martin
Marie-Thérèse
MT
Ramanitrahasimbola
David
D
Rasoanaivo
Philippe
P
Brocard
Jacques
J
D000470:Alkaloids / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D001769:Blood / Q000469:parasitology; D002738:Chloroquine / Q000494:pharmacology*; D004347:Drug Interactions; D004351:Drug Resistance / Q000187:drug effects; D005290:Ferric Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000962:Antimalarials; D005290:Ferric Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; C501169:Na-deacetyl-ferrocenoyl-strychnobrasiline; C103767:strychnobrasiline; D002738:Chloroquine