Antiplasmodial activity of aspidosperma indole alkaloids.
The antiplasmodial activity of twelve alkaloids with an aspidospermane skeleton was estimated in vitro on chloroquine-resistant and sensitive strains of Plasmodium falciparum. Seven tetracyclic alkaloids possessing a free ethyl chain such aspidospermine, showed IC50 after incubation for 72 h between 3.2 and 15.4 microM. Moreover, four pentacyclic alkaloids with ethyl chain included in a tetrahydrofuran, such haplocine, showed a reduced activity, with IC50, after 72 h, between 22.6 and 52.6 microM. According to these results, a chloroquine-potentiating experiment was also performed with two of the most active compounds. Isobolograms were obtained and demonstrated a synergic effect of N-formyl-aspidospermidine and aspidospermine when associated with chloroquine. The cytotoxicity and the selectivity index of some alkaloids were also estimated.
Mitaine-Offer
A C
AC
Laboratoire de Pharmacognosie, Faculté de Pharmacie, Université de Reims Champagne-Ardenne, France. acoffer@u-bourgogne.fr
Sauvain
M
M
Valentin
A
A
Callapa
J
J
Mallié
M
M
Zèches-Hanrot
M
M
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D030009:Aspidosperma; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
D000470:Alkaloids; D000962:Antimalarials; D026121:Indole Alkaloids; D007211:Indoles; D010936:Plant Extracts; D011804:Quinolines; D019271:Hypoxanthine; D002738:Chloroquine; C091896:aspidospermine