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

被引：28

作者：

Búa, J ^{[1
]}

Ruiz, AM ^{[1
]}

Potenza, M ^{[1
]}

Fichera, LE ^{[1
]}

机构：

[1] Consejo Nacl Invest Cient & Tecn, Inst Nacl Parasitol Dr Mario Fatala Chaben ANLIS, RA-1063 Buenos Aires, DF, Argentina

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 18期

关键词：

trypanocidal; cyclophilin; cyclosporin A; peptidyl-prolyl cis-trans isomerase;

D O I：

10.1016/j.bmcl.2004.07.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Cyclosporin A (CsA) nonimmunosuppressive analogs were evaluated against Trypanosoma cruzi and on TcCyP19, a cyclophilin of 19kDa. 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 muM, respectively, compared to CsA IC50 value 5.39 muM on epimastigote proliferation; and on trypomastigote lysis their IC50 values were 0.97 and 2.66 muM compared to CsA IC50 value 7.19 muM. 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. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4633 / 4637

页数：5

共 24 条

[1]

Substitution in position 3 of cyclosporin A abolishes the cyclophilin-mediated gain-of-function mechanism but not immunosuppression [J].