Búa Jacqueline, Ruiz Andrés M, Potenza Mariana, Fichera Laura E
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.
Bioorg Med Chem Lett. 2004 Sep 20;14(18):4633-7. doi: 10.1016/j.bmcl.2004.07.003.
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.
对环孢素A（CsA）的非免疫抑制类似物进行了抗克氏锥虫以及针对19 kDa亲环蛋白TcCyP19的评估。在八项CsA类似物中，有两项，即H-7-94和F-7-62在所有体外试验中显示出最佳的抗寄生虫效果。它们的半数抑制浓度（IC50）值分别为0.82和3.41微摩尔，相比之下，CsA对无鞭毛体增殖的IC50值为5.39微摩尔；在对锥鞭毛体裂解试验中，它们的IC50值分别为0.97和2.66微摩尔，而CsA的IC50值为7.19微摩尔。在抑制锥鞭毛体感染方面，H-7-94和F-7-62也比CsA更有效。所有CsA衍生物均抑制了TcCyP19的酶活性，表明该靶点参与了所观察到的杀锥虫作用。
