In Vitro Plasmodium falciparum Drug Sensitivity Assay: Inhibition of Parasite Growth by Incorporation of Stomatocytogenic Amphiphiles into the Erythrocyte Membrane

摘要: Lupeol, which shows in vitro inhibitory activity against Plasmodium falciparum 3D7 strain with a 50% concentration (IC50) of 27.7 +/- 0.5 microM, was shown to cause transformation the human erythrocyte shape toward that stomatocytes. Good correlation between IC50 value and membrane curvature changes caused by lupeol observed. Preincubation erythrocytes lupeol, followed extensive washing, made cells unsuitable for parasite growth, suggesting compound incorporates into irreversibly. On other hand, lupeol-treated culture continued grow well untreated erythrocytes. Thus, antiplasmodial appears be indirect, being due stomatocytic host cell not toxic effects via action on drug target within parasite. A number amphiphiles stomatocyte formation, but those causing echinocyte were inhibit growth parasites, apparently mechanism similar lupeol. Since agents through modifications must regarded as leads development new antimalarial drugs, care exercised interpretation results screening plant extracts natural product libraries an toxicity assay.