Effects of nitroheterocyclic drugs on macromolecule synthesis and degradation in Trypanosoma cruzi.

Nifurtimox and benznidazole, two nitroheterocyclic drugs, inhibited DNA, RNA and protein synthesis, stimulated macromolecular degradation, and stimulated unscheduled DNA synthesis in Trypanosoma cruzi (Tulahuen strain). Significant differences in the mode of action of these drugs could be established and, in every case, nifurtimox was more active than benznidazole. The inhibition of macromolecular synthesis varied with drug concentration, precursor and incubation time. Nifurtimox effect was time dependent and irreversible. When assayed on macromolecular degradation, nifurtimox was more effective on DNA and protein than on RNA, while benznidazole displayed almost the same activity on DNA, RNA and protein. Labeling of RNA with [3H]uridine in the presence of nifurtimox followed atypical kinetics since, depending on incubation time and concentration, RNA degradation prevailed over RNA synthesis.