3'-脱氧-3'-氟肌苷作为一种有效的抗利什曼原虫剂。3'-脱氧-3'-氟肌苷对热带利什曼原虫和杜氏利什曼原虫在体外和体内的代谢及选择性细胞毒性作用。

3'-Deoxy-3'-fluoroinosine as a potent antileishmanial agent. The metabolism and selective cytotoxic effect of 3'-deoxy-3'-fluoroinosine against Leishmania tropica and L. donovani in vitro and in vivo.

作者信息

Shin I S, Tanifuji H, Arata Y, Morizawa Y, Nakayama T, Wataya Y

机构信息

Faculty of Pharmaceutical Sciences, Okayama University, Japan.

出版信息

Parasitol Res. 1995;81(7):622-6. doi: 10.1007/BF00932030.

DOI:10.1007/BF00932030

PMID:7479655

Abstract

We studied the antileishmanial activity of 3'-deoxy-3'-fluoroinosine (3'-FI) against Leishmania tropica and L. donovani. In in vitro cultivation, the EC50 values (the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value) obtained for 3'-FI against the promastigotes of L. tropica and L. donovani were 2.3 x 10(-7) and 1.0 x 10(-6) M, respectively. It was less toxic toward mouse mammary-tumor FM3A cells, a model host; the EC50 value was 1.9 x 10(-4) M. Leishmania promastigote metabolized 3'-FI to 3'-deoxy-3'-fluoroadenosine 5'-triphosphate (3'-FATP) but FM3A cells did not. 3'-FI was effective against L. donovani amastigotes in J774.1 cells in an in vitro cultivation system under conditions similar to those used in the in vivo assay. 3'-FI (50 mg/kg, given i.v.) showed a cytotoxic effect against the amastigotes of L. donovani in mice.

摘要

我们研究了3'-脱氧-3'-氟肌苷（3'-FI）对热带利什曼原虫和杜氏利什曼原虫的抗利什曼活性。在体外培养中，3'-FI对热带利什曼原虫和杜氏利什曼原虫前鞭毛体的半数有效浓度（EC50值，即抑制细胞生长速率至对照值50%所需的药物浓度）分别为2.3×10⁻⁷和1.0×10⁻⁶ M。它对模型宿主小鼠乳腺肿瘤FM3A细胞的毒性较小；EC50值为1.9×10⁻⁴ M。利什曼原虫前鞭毛体将3'-FI代谢为3'-脱氧-3'-氟腺苷5'-三磷酸（3'-FATP），但FM3A细胞不会。在类似于体内试验的条件下，3'-FI在体外培养系统中对J774.1细胞内的杜氏利什曼原虫无鞭毛体有效。静脉注射3'-FI（50 mg/kg）对小鼠体内的杜氏利什曼原虫无鞭毛体具有细胞毒性作用。