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.
Faculty of Medicine, University of Papua New Guinea, Boroko, NCD.
D L
DL
Wesche
J
J
Black
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