ASSAYS OF EFFICACY ON TRYPANOSOMA-BRUCEI- BRUCEI WITH DRUGS PASSING THROUGH THE BLOOD-BRAIN-BARRIER AND THE MEGAZOL

Human African trypanosomiasis (HAT) is a major public health problem i n 36 sub-Saharan African countries and around 50 million people are cl assed as ''at risk''. About 25,000 new cases of the disease are report ed annually by the World Health Organisation (WHO). This disease is fa tal if untreated. As for now chemotherapy is unsatisfactory and relies on a few drugs which show two major problems. The first is pharmacoki netics involving the passage through the blood-brain barrier. The seco nd concerns toxicity and adverse side-effects of drugs used to treat t his disease. New trypanocides should be safe, effective without toxici ty. This study reports the action of 45 drugs, known to pass through t he blood-brain barrier and belonging to different therapeutic classes, and also the megazol, a nitrothiadiazole derivative, on Trypanosoma b rucei brucei An Tat 1-9 in vitro in acellular semi-defined medium. Res ults showed that some drugs did not modify the parasitic growth, and o thers were either trypanostatic or trypanocide. These last drugs were tested in vivo on T. b. brucei An-Tat 1-9 infected Swiss mice. Only me gazol was shown to be effective and trypanocide. This compound might t rigger the production of oxygen derivatives and free radicals which ha ve toxic effects on the trypanosome metabolism.