THE EFFICACY OF BENZIMIDAZOLE DRUGS AGAINST PLASMODIUM-FALCIPARUM IN-VITRO

The sensitivities in vitro of Plasmodium falciparum to the benzimidazo les, albendazole, thiabendazole, mebendazole, omeprazole and 2 albenda zole metabolites, albendazole sulphone and albendazole sulphoxide, wer e investigated and compared to those of the commonly used antimalarial drugs chloroquine and quinine. Quinine and chloroquine were the most potent drugs tested (EC50 values of 8x10(-9)-6x10(-8) mol/L and 5-7x10 (-9) mol/L, respectively). Thiabendazole, mebendazole, albendazole sul phone and albendazole sulphoxide reached maximum growth inhibitions of 13-36% at the highest concentration tested (1x10(-4) mol/L). Albendaz ole (EC50 range: not achieved-2x10(-6) mol/L) and omeprazole (EC50 ran ge: 2-4x10(-5) mol/L) were the most effective benzimidazoles. The acti vity of albendazole was pH dependent, as was that of chloroquine, and variable. Albendazole has its primary mode of action on trophozoites, suggesting that the drug may target parasite tubulin polymerization. O meprazole, although also primarily effective against trophozoites, had additional activity against schizonts and ring forms, suggesting a di stinct or additional parasitic target. Given the variable activity of albendazole and its rapid metabolism in vivo into compounds with even less antimalarial activity, it appears unlikely that this benzimidazol e will be useful in the treatment of malaria. The rapid activity and d ifferent stage-specific profile of the more soluble benzimidazole omep razole warrants further investigation.