Abstract
The effect of 2-pyridinecarboxylic acid (picolinic acid) on trypanosomes of the subgenus Schizotrypanum isolated from the bat Phyllostomus hastatus was determined in this study. Picolinic acid, at 50 µg mL-1, inhibited epimastigote growth by 99% after 12 days incubation. In addition, trypomastigote motility decreased by 50% after 6h and completely after 24h in the presence of 50 µg mL-1 picolinic acid. The 50% cytotoxic concentration on HEp-2 cell line was 275 µg mL-1 after 4 days incubation. Altogether, these results indicate higher toxicity against trypanosomes. The inhibitory effect of picolinic acid on epimastigote growth can be partially reversed by nicotinic acid and L-tryptophan, suggesting a competitive inhibition. Furthermore, two anti-Trypanosoma (Schizotrypanum) cruzi drugs were also evaluated with regard to bat trypanosome growth. Benznidazole, at 50 µg mL-1, inhibited epimastigote growth by 90% after 12 days incubation. Nifurtimox, at the same concentration, caused 96% growth inhibition after four days incubation. Corroborating a previous study, bat trypanosomes are a good model for screening new trypanocidal compounds. Moreover, they can be used to study many biological processes common to human pathogenic trypanosomatids.
Highlights
The subgenus Schizotrypanum includes several trypanosome species that are difficult to discriminate morphologically (HOARE, 1972)
Bat trypanosomes can be separated into three distinct groups using genetic markers - two from Europe (Trypanosoma dionisii and Trypanosoma vespertilionis) and one from the Americas (Trypanosoma marinkellei)
The latter is more related to T. (S.) cruzi than the European isolates (BAKER et al, 1978; BARNABE et al, 2003), but as mentioned, bat trypanosomes do not grow under conditions that exist in humans (BAKER et al, 1978; HAMANAKA; PINTO, 1993; PINTO et al, 1987)
Summary
The subgenus Schizotrypanum includes several trypanosome species that are difficult to discriminate morphologically (HOARE, 1972). Whereas Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas’ disease, infects humans and a wide variety. There is no vaccine against T. cruzi infection, and the currently available drugs (nifurtimox and benznidazole) are active in acute or short-term chronic infections but have limited efficacy during the chronic phase of the disease (URBINA; DOCAMPO, 2003). Both drugs have severe side-effects which can lead to discontinuation of treatment, and strains that are naturally resistant to them have been reported (FILARDI; BRENER, 1987; LÉON-PÉREZ et al, 2007). T. cruzi develops benznidazole resistance during experimental infection in mice (SANTOS et al, 2008). There is a need for the development of new and more efficacious anti-T. (S.) cruzi drugs
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