Trypanocidal action of 2,4-dichloro-6-phenylphenoxyethyl diethylamine hydrobromide (Lilly 18947) on Trypanosoma cruzi  

氢溴酸2,4-二氯-6-苯基苯氧乙基二乙基胺(Lilly18947)抗克氏锥虫的作用

作　　者：Adriana Silvina BERNACCHI Berta FRANKE de CAZZULO Jose Alberto CASTRO Juan Jose CAZZULO 

机构地区：[1]Centro de Investigations Toxicologicas,CEITOX-CITEFA/CONICET,J B de La Salle 4397,1603 Villa Martelli,Provincia de Buenos Aires,Argentina

出　　处：《Acta Pharmacologica Sinica》2002年第5期399-404,共6页中国药理学报(英文版)

基　　金：Supported by Grant from the Secretaria de Tecnologia,Ciencia e Innovacion Productiva.Argentina.Grant:PICT 1997.

摘　　要：AIM:To study the effect of the inhibitor of cytochrome P450 known as Lilly 18947(2,4 dichloro-6 phenyl-phenoxy ethyl diethylamine)on Trypanosoma cruzi.METHODS:Trypanosoma cruzi epimastigotes wen grown in culture,in absence or in presence of drug.The inhibition of its growth was followed by daily counting using a Neubauer chamber.The effect of Lilly 18947 on the parasite ultrastructure was examined by electron microscopy.To test the effect of different concentrations of drug on the parasite cycle,Vero cells were inoculated with trypomastigotes(RA strain)and after 72 h the percentage of infected cells and the number of intracellular parasites were estimated and expressed as the endocytic index.RESULTS:Growth of epimastigotes was inhibited by Lilly 18947.Concentrations as low as 50μmol/L resulted in a complete disappearance of the parasites in culture by the fourth day.With lower concentrations,little growth was observed and total(25μmol/L)or partial lysis(10μmol/L)were registered by the eighth day of culture.Incubation of epimastigotes with 50μmol/L of Lilly 18947 resulted in an early damage to cellular structures.Initial signs were dilatation of perinuclear membranes and mitochondria swelling.The infectivity of trypomastigotes to Vero cells in culture was nearly abolished at 15 and 30μmol/L concentrations of the drug.CONCLUSION:Lilly 18947 was able to harm Trypanosoma cruzi membranefunctions leading to the loss of its infective properties and its death.

关 键 词：Lilly 18947 Trypanosoma cruzi trypanocidal agents Vero cells 

分 类 号：R96[医药卫生—药理学]