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Mode of action of tubulozoles against Plasmodium falciparum in vitro

The mode of action of the tubulozole isomers, recently recognized as a new class of potential antimalarial agents, was investigated. Whereas neither glycolysis, protease activity, or nucleic acid biosynthesis was primarily affected, protein biosynthesis decreased soon after addition of the drug. Inhibitors of protein biosynthesis, however, did not show synergistic activity with tubulozole. Colcemid, on the other hand, had an effect on protein synthesis similar to that seen with the tubulozoles. Furthermore, combinations of the tubulozole isomers with compounds known to interact with tubulin inhibited malaria in a synergistic or antagonistic fashion. Therefore, the inhibition might be elicited by interaction with tubulin or some other component of the microtubules. This is remarkable insofar as only one of the tubulozole isomers affects mammalian cells by binding to tubulin.