Premium
Pyrazinoates as antiparasitic agents against Trypanosoma cruzi
Author(s) -
Vasconcelos Camilla I.,
Varela Marina T.,
Torrecilhas Ana C.,
Fernandes João P. S.
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800190
Subject(s) - benznidazole , trypanosoma cruzi , antiparasitic , antiparasitic agent , cytotoxicity , chagas disease , nifurtimox , chemistry , antimycobacterial , pharmacology , biology , biochemistry , in vitro , virology , parasite hosting , medicine , mycobacterium tuberculosis , tuberculosis , pathology , world wide web , computer science
This work reports a repurposing study of pyrazinoic acid ( 1 ) and methyl ( 2 ), ethyl ( 3 ) and 2‐chloroethyl ( 4 ) ester derivatives with antimycobacterial activity, in assays against Trypanosoma cruzi . The compounds and benznidazole, the standard antitrypanosoma drug, were evaluated in concentrations ranging from 100 to 6.25 μg/mL. The results showed that compounds 2 and 3 (EC 50 = 182 and 447 μM) significantly reduced the infection rate of the parasite into the mammalian cells at 100 μg/mL ( p < 0.05) in a similar way to benznidazole. In addition, all the compounds also significantly reduced the number of intracellular parasites (compound 1 at 50 μg/mL, and compounds 2–4 at 100 μg/mL, p < 0.05) in comparison to the control. Compounds 1 and 2 were more effective than benznidazole at 50 μg/mL ( p < 0.001). Moreover, compounds 1–4 did not show significant cytotoxicity against THP‐1, J774, and HeLa cells (>1000 μM), indicating that they possess considerable selectivity against the parasites. This report represents the first study of such compounds against T. cruzi , indicating the potential of pyrazinoates as antiparasitic agents.