Abstract:

【Abstract】 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 (1-105 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 103 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 >104 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.