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 IC(50) values were 0.82 and 3.41 microM, respectively, compared to CsA IC(50) value 5.39 microM on epimastigote proliferation; and on trypomastigote lysis their IC(50) values were 0.97 and 2.66 microM compared to CsA IC(50) value 7.19 microM. 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.
Instituto Nacional de Parasitología 'Dr. Mario Fatala Chabén' ANLIS Carlos G. Malbrán; Consejo Nacional de Investigaciones, Científicas y Técnicas. Av. Paseo Colón 568 (1063) Buenos Aires, Argentina. jacbua@yahoo.com
Jacqueline
J
Búa
Andrés M
AM
Ruiz
Mariana
M
Potenza
Laura E
LE
Fichera
D000818:Animals; D002522:Chlorocebus aethiops; D021983:Cyclophilins / Q000037:antagonists & inhibitors / Q000378:metabolism; D003524:Cyclosporins / Q000737:chemistry / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D014709:Vero Cells
D003524:Cyclosporins; C497002:F-7-62 cyclosporin; C497001:H-7-94 cyclosporin; D007166:Immunosuppressive Agents; D014344:Trypanocidal Agents; C431607:cyclophilin 19; D021983:Cyclophilins