In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T-congolense

The effect of 34 alkaloids of the piperidine, pyridine, tropane, isoquinoli ne, indole, quinolizidine, quinoline, purine, and steroidal types on the gr owth of Tryponosoma brucei, T congolense, and human HL-60 cells was investi gated in vitro. Berbamine, berberine, cinchonidine, cinchonine, emetine, er gotamine, quinidine, quinine, and sanguinarine showed trypanocidal activiti es with ED50 (50% effective dose) values below 10 muM. Berberine, emetine, and quinidine were the most active compounds found; their ED50 values and m inimum inhibitory concentrations were comparable to those of the antitrypan osomal drugs suramin and diminazene aceturate. However, most of these compo unds were also cytotoxic. In the case of emetine, the ratio of cytotoxic/tr ypanocidal activity was only 3 while for quinidine it was 300 indicating th at this alkaloid could be a candidate for further drug development. DNA int ercalation in combination with protein biosynthesis inhibition, which is th e major mode of action of the active alkaloids, could be responsible for th e observed trypanocidal and cytotoxic effects.