[An efficacy trial on Trypanosoma brucei brucei of molecules permeating the blood-brain barrier and of megazol].
Human African trypanosomiasis (HAT) is a major public health problem in 36 sub-Saharan African countries and around 50 million people are classed as "at risk". About 25,000 new cases of the disease are reported annually by the World Health Organisation (WHO). This disease is fatal if untreated. As for now, chemotherapy is unsatisfactory and relies on a few drugs which show two major problems. The first is pharmacokinetics involving the passage through the blood-brain barrier. The second concerns toxicity and adverse side-effects of drugs used to treat this disease. New trypanocides should be safe, effective without toxicity. This study reports the action of 45 drugs, known to pass through the blood-brain barrier and belonging to different therapeutic classes, and also the megazol, a nitrothiadiazole derivative, on Trypanosoma brucei brucei AnTat 1-9 in vitro in acellular semi-defined medium. Results showed that some drugs did not modify the parasitic growth, and others were either trypanostatic or trypanocide. These last drugs were tested in vivo on T. b. brucei An-Tat 1-9 infected Swiss mice. Only megazol was shown to be effective and trypanocide. This compound might trigger the production of oxygen derivatives and free radicals-which have toxic effects on the trypanosome metabolism.
D017954:Africa South of the Sahara; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D003470:Culture Media; D004195:Disease Models, Animal; D005260:Female; D005609:Free Radicals / Q000494:pharmacology; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013830:Thiadiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000145:classification / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy; D014944:World Health Organization
D003470:Culture Media; D005609:Free Radicals; D017382:Reactive Oxygen Species; D013830:Thiadiazoles; D014344:Trypanocidal Agents; C013378:megazol
Essais d'efficacité sur Trypanosoma brucei brucei de molécules franchissant la barrière hématoméningée et du mégazol.