Andrés Rivadulla Rodríguez

Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi.

Proteins rich in sulfhydryl groups, such as metallothionein, are present in several strains of the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. Metallothionein-like protein concentrations ranged from 5.1 to 13.2 pmol/mg protein depending on the parasite strain and growth phase. Nifurtimox and benznidazole, used in the treatment of Chagas disease, decreased metallothionein activity by approximately 70%. T. cruzi metallothionein was induced by ZnCl2. Metallothionein from T. cruzi was partially purified and its monobromobimane derivative showed a molecular weight of approximately 10,000 Da by SDS-PAGE analysis. The concentration of trypanothione, the major glutathione conjugate in T. cruzi, ranged from 3.8 to 10.8 nmol/mg protein, depending on the culture phase. The addition of buthionine sulfoximine to the protozoal culture considerably reduced the concentration of trypanothione and had no effect upon the metallothionein concentration. The possible contribution of metallothionein-like proteins to drug resistance in T. cruzi is discussed.

Effects of 3-chloro-phenyl-1,4-dihydropyridine derivatives on Trypanosome cruzi epimastigotes

A series of 3-chloro-phenyl-1,4-dihydropyridine derivatives produced different degrees of inhibition of parasite growth and respiration on clone Brener, LQ and Tulahuen strains of Trypanosome cruzi epimastigotes. Respiratory chain inhibition appears to be a posible determinant of the trypanosomicidal activity of this compounds. No difference in the action of these derivatives was found among the different parasite strains. For comparative purposes, the inhibitory effects of felodipine and nicardipine are also reported. A good correlation between toxic effects and the easiness of oxidation of the dihydripyridine ring was found. The presence of a fused ring on the dihydropyridine moiety significantly diminished the inhibitory effects.