In vitro anti-parasitic activity of Cyclosporin A analogs on Trypanosoma cruzi

Cyclosporin A (CsA) nonimmunosuppressive analogs were evaluated against Trypanosoma cruzi and on TcCyP19, a cyclophilin of 19 kDa. Two out of eight CsA analogs, H-7-94 and F-7-62 showed the best anti-parasitic effects on all in vitro assays. Their IC50 values were 0.82 and 3.41 μM, respectively, compared to CsA IC50 value 5.39 μM on epimastigote proliferation; and on trypomastigote lysis their IC50 values were 0.97 and 2.66 μM compared to CsA IC50 value 7.19 μM. H-7-94 and F-7-62 were also more effective than CsA in inhibiting trypomastigote infection. The enzymatic activity of TcCyP19 was inhibited by all CsA derivatives, suggesting this target is involved in the trypanocidal effects observed.