Objective: To investigate the antimalarial activity of four choline derivatives against Plasmodium falciparum 3D7 strain growth in vitro.
Methods: Four choline derivatives MD [N-dodecyl-N-(2-hydroxyethyl)-N,N- dimethyl ammonium bromide], ED [N-dodecyl-N-(2-hydroxyethyl)-N,N-diethyl ammonium bromide], MT [N-tetradecyl-N- (2-hydroxyethyl)-N,N-dimethyl ammonium bromide], and ET [N-tetradecyl-N-(2-hydroxyethyl)-N,N-diethyl ammonium bromide] were dissolved separately in DMSO at serial concentrations (1-10(5) µmol/L). The solutions were diluted by 1,000-fold with RPMI 1640 medium. 20 µl drug-containing medium and 80 µl P. falciparum-infected erythrocyte suspension (2% final hematocrit and 0.3%-0.5% parasitemia) were added to each well of microtiter plates. Drug effect on the in vitro growth of P. falciparum was measured by SYBR Green I method. The half maximal inhibitory concentration (IC50) was calculated from dose-response curves. Artemisinine served as positive control.
Results: Artemisinine, MD, ED, MT, and ET showed different degrees of dose-dependent inhibition on P. falciparum growth. When the MD concentration was above 10 nmol/L, the inhibition rate increased significantly. Both ED and ET showed significant inhibitory effects at high concentrations, with inhibition rate of > 95% when their doses were > 10(4) nmol/L. The IC50 values of MD, ED, MT, and ET were 1 620, 33.9, 116, and 68.9 nmol/L, respectively, all significantly higher than that of artemisinine (5.7 nmol/L) (P < 0.05).
Conclusion: The four choline derivatives show certain antimalarial activity, which is lower than that of artemisinine. Among the four derivatives, ED has the strongest antimalarial activity against P. falciparum 3D7 strain.