Effect of quinones and nitrofurans on Trypanosoma mega and Crithidia fasciculata

: Demonstration of trypanocidal effects in vitro is a first step for the development of new antichagasic drugs. In order to obtain an experimental model allowing the pre-screening of potential trypanocides for Trypanosoma cruzi in a short time and under safe conditions, the trypanosomatids T. mega and C. fasciculata were assayed for their response to a) compounds known for their action on T. cruzi, and b) compounds not tested before on the latter. The drugs were assayed on the organisms growth in a liquid culture medium, cell multiplication being measured by the medium turbidity increase, using a photoelectric colorimeter previously calibrated with cell suspensions of known concentration. A series of quinones (Lapachones and related compounds), naftoquinone-imines, benzoquinones (perezone and dihydroperezone), a quinol (miconidine) and several nitrofurans, including nifurtimox and (5-nitro-2-furfurylidene)-amino (NF-group) derivatives, inhibited the flagellates growth, specially T. mega, with half-maximal inhibitory concentrations lesser than 5.0 microM, for the most active compounds. T. mega response to nifurtimox, NF-derivatives and beta-lapachone was in close agreement with that of T. cruzi. Cultures of T. mega in the presence of NF-pyrazole, NF-indazoles and NF-imidazole but not nifurtimox, showed irreversible damage since, after re-incubation in fresh medium without inhibitor, these cells grew significantly less than their corresponding controls. Similar effects were observed in C. fasciculata, with beta-lapachone and one naftoquinone-imine. Our results qualify T. mega as an adequate experimental model for the assay of antichagasic agents, as C. fasciculata and T. brucei brucei do for the african trypanosomes.