Authors

Discussion

Animal African trypanosomiasis (or nagana) is a wasting disease caused by protozoan trypanosomes Trypanosoma congolense, T. vivax and T. brucei. Transmitted by haematophagous flies, these parasites cause high morbidity, mortality and infertility in livestock, with disastrous effects on Africa's rural economy. As resistance to the few compounds licensed to treat and prevent infection soars, the quest for efficacious alternatives becomes a critical research priority.

Following evidence of good activity against the three aetiological agents of nagana, we are currently progressing a series of DNA minor groove binders (S-MGBs). In vivo activity was demonstrated for selected S-MGBs in a standard T. congolense mouse model. No indications of cross-resistance to the currently used drug diminazene aceturate have emerged, and the S-MGBs also retained their activity against parasites resistant to the other veterinary trypanocides isometamidium chloride and homidium bromide. Although the S-MGBs are believed to target the parasite's DNA, their specific MOA is still unclear. After treatment with high doses, partial inhibition of DNA synthesis and changes in the nucleotide pool were observed, along with an accumulation of parasites with multiple nuclei and kinetoplasts, indicative of a cytokinesis block. Whether these are direct or indirect effects of the S-MGBs is under investigation.