A comparison of the antimalarial activity of the cinchona alkaloids against Plasmodium falciparum in vitro.
The effects of four major cinchona alkaloids: (-) quinine, (+) quinidine, (-)cinchonidine, and (+)cinchonine against Plasmodium falciparum FCQ-27/PNG were studied. The alkaloids were tested in vitro as either single alkaloids, racemic mixtures of stereoisomers, or as an equimolar combination of all four alkaloids. Results indicate (+)quinidine to be most effective and both (+)stereoisomers were more potent than the (-)stereoisomers. Inhibitory concentrations 50% (Ki) of racemic mixtures of stereoisomers were similar to those of the (+)stereoisomers alone. The Ki of four alkaloids in equimolar combination were similar to that of the (-) cinchonidine/(+)cinchonine racemic mixture. A total alkaloidal extract of Cinchona sp. was tested and compared with the pure alkaloids. HPLC analysis indicated that (+)cinchonine, (-)cinchonidine and (-)quinine were present in a ratio of approximately 1:1:2, respectively. The total alkaloid extract, with (-)stereoisomers predominating, was less effective than the four alkaloids in combination. The nature of the interaction between stereoisomers was investigated and appears to be one of addition.
Wesche
D L
DL
Faculty of Medicine, University of Papua New Guinea, Boroko, NCD.
Black
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002930:Cinchona Alkaloids / Q000032:analysis / Q000494:pharmacology*; D004338:Drug Combinations; D007536:Isomerism; D010963:Plasmodium falciparum / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology
D002930:Cinchona Alkaloids; D004338:Drug Combinations; D011803:Quinine; D011802:Quinidine