Pyrazinoates as antiparasitic agents against Trypanosoma cruzi. Issue 11 (9th October 2018)

• Record Type: Journal Article
• Authors: Vasconcelos, Camilla I.; Varela, Marina T.; Torrecilhas, Ana C.; Fernandes, João P. S.
• Is Part Of: Archiv der Pharmazie. Volume 351:Issue 11(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-10-09
• Subjects: antichagasic -- antitrypanosoma agents -- drug repositioning -- pyrazinoates; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201800190
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: 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 compounds2 and3 (EC50 = 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 (compound1 at 50 μg/mL, and compounds2–4 at 100 μg/mL, p < 0.05) in comparison to the control. Compounds1 and2 were more effective than benznidazole at 50 μg/mL ( p < 0.001). Moreover, compounds1–4 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. Abstract : Pyrazinamide, an antimycobacterial agent, was also reported as anti‐ Leishmania agent, whereas its active form, pyrazinoic acid, and its esters were reported as antimycobacterial agent with no other activity described to date. Here, the evaluation of pyrazinoic acid and some esters against Trypanosoma cruzi is reported, showing that methyl pyrazinoate has comparable activity to benznidazole, with low cytotoxicity to mammalian cells.