Trypanocidal action of neuroleptic phenothiazines in Trypanosoma brucei

This paper reports the effects of a series of phenothiazine derivatives on trypanosomes in vitro. Our results demonstrate that trypanosomes are very sensitive to some of these compounds at micromolar concentrations. Electron microscopic analysis of drug-treated cells shows that the pellicular layer of microtubules is selectively disintegrated by phenothiazine treatment, while the flagellar axoneme is entirely resistant to the drug. These observations suggest that phenothiazines might constitute a promising candidate group for the development of new trypanocidal drugs. Furthermore, they indicate that the mechanism of drug action is mediated through a specific interaction of phenothiazines with the pellicular, but not with the flagellar, microtubules.