With the re-emergence of Human
African Trypanosomiasis (HAT) on the one hand, which are increasingly resistant to current
therapies, and the stage-dependent effectiveness or even the prohibitive cost of these
therapies on the other hand,
megazol, a
5-nitroimidazole thiadiazole highly active against various trypanosomal species, was assessed for its genotoxic potential. Very little information has become available until now. Two batches of
megazol were provided by two different suppliers: Far-Manguinhos, a part of the Fiocruz foundation, under the Brazilian Minister of Health, and Delphia, a French company. These two batches, obtained by different synthetic routes, were studied by means of the in vitro micronucleus assay on L5178Y mouse
lymphoma cells, in its microscale version. Both batches of magazol displayed a strong genotoxic activity in this screening assay. A second batch from Delphia was then investigated by use of two tests, i.e. the in vitro metaphase analysis with human lymphocytes and the in vivo micronucleus test in rat bone-marrow.
Megazol was shown to be a potent inducer of in vitro and in vivo
chromosomal aberrations. Although
megazol is a potent trypanocidal agent and is orally bio-available, its toxicity dictates that it should not be developed further for the treatment of HAT and
Chagas disease. All development work has therefore been discontinued.