In Vitro Effect of Alkaloids on Bloodstream Forms of Trypanosoma brucei and T. congolense

Abstract

The effect of 34 alkaloids of the piperidine, pyridine, tropane, isoquinoline, indole, quinolizidine, quinoline, purine, and steroidal types on the growth of Trypanosoma brucei, T. congolense, and human HL-60 cells was investigated in vitro. Berbamine, berberine, cinchonidine, cinchonine, emetine, ergotamine, quinidine, quinine, and sanguinarine showed trypanocidal activities with ED₅₀ (50 % effective dose) values below 10 μM. Berberine, emetine, and quinidine were the most active compounds found; their ED₅₀ values and minimum inhibitory concentrations were comparable to those of the antitrypanosomal drugs suramin and diminazene aceturate. However, most of these compounds were also cytotoxic. In the case of emetine, the ratio of cytotoxic/trypanocidal activity was only 3 while for quinidine it was 300 indicating that this alkaloid could be a candidate for further drug development. DNA intercalation in combination with protein biosynthesis inhibition, which is the major mode of action of the active alkaloids, could be responsible for the observed trypanocidal and cytotoxic effects.

Key words

Alkaloids - African trypanosomes - HL-60 cells - antitrypanosomal activity - DNA intercalation - inhibition of protein biosynthesis

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