Ketoconazole and other potent antimycotic azoles exhibit pronounced activity againstTrypanosoma cruzi, Plasmodium berghei andEntamoeba histolytica in vivo
Ketoconazole and other potent antimycotic azoles exhibit pronounced activity againstTrypanosoma cruzi, Plasmodium berghei andEntamoeba histolytica in vivo
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酮康唑和其他有效的抗真菌唑类药物在体内对克氏锥虫、伯氏疟原虫和溶组织内阿米巴表现出显着的活性
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发表时间：
2004
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通讯作者：
H. Seidenath
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作者：
W. Raether;H. Seidenath
咪唑类抗真菌药物酮康唑（Heeres埃塔尔1979）、H 82 5338和S 82 5183（Raether和Dittmar，未发表的数据）和三唑衍生物ICI 153，066（赖利和威尔逊1982）在动物口服给药后对局部和全身真菌感染（皮肤癣菌、多相真菌、酵母菌）高度有效。令人惊讶的是，已经上市的酮康唑（KETO）对利什曼原虫（Berman 1982; Urcuyo和Zaias 1982）和氯喹耐药恶性疟原虫（Pfaller和Krogstad 1981）非常有效。因此，与相应的标准药物以及对其他致病性原生动物的比较，研究KETO是有意义的。我们能够证实该药物对金黄仓鼠中的杜氏利什曼原虫具有显著作用，我们还发现该药物对小鼠中的伯氏疟原虫以及金黄仓鼠肠外阿米巴病模型中的溶组织内阿米巴具有显著活性（见表1）。相比之下，在感染弓形虫、布氏锥虫或胎儿三毛滴虫的小鼠和感染柔嫩艾美耳球虫的鸡中，KETO无活性（见表1）。由于Keto对组织形式的L. donovani，我们假设抗霉唑类药物对克氏锥虫也有全身作用。因此，我们调查了KETO，H 82 5338，-（2 - 1，2，3，4-四氢异喹啉-6-基）-醚，S 82 5183，2-（咪唑基-1-甲基）-2-（2，4-二氯苯基）1，3-二氧戊环-4-基< 4-甲氧基（吗啉代-亚甲基-苯胺）和ICI 153，066，2-（1，2，4-三唑-1-基）-1-（4-氟苯基）-1-（2，4-二氯苯基）-乙醇。cruzi（关于材料和方法的详细信息，参见Raether和Seidenath 1983）。
The imidazole antimycotic drugs, ketoconazole (Heeres etal. 1979), H 82 5338 and S 82 5183 (Raether and Dittmar, unpublished data) and the triazole-derivative ICI 153,066 (Ryley and Wilson 1982) are highly effective against topic and systemic fungal infections (dermatophytes, multiphasic fungi, yeasts) after oral administration in animals. Surprisingly, ketoconazole (KETO), which is already on the market, is remarkably effective against leishmania (Berman 1982; Urcuyo and Zaias 1982) and chloroquine resistant Plasmodium falciparum (Pfaller and Krogstad 1981). It was therefore of interest to investigate KETO in comparison with corresponding standard drugs as well as against other pathogenic protozoa. We were able to confirm the pronounced action of the drug against Leishmania donovani in the golden hamster, and we also found a marked activity against Plasmodium berghei in the mouse as well as against Entamoeba histolytica in the extraintestinal amoebiasis model in the golden hamster (see Table 1). In contrast, KETO was inactive in mice infected with Toxoplasma gondii, Trypanosoma brucei or Tritrichomonas foetus and in chickens infected with Eimeria tenella (see Table 1). Because of the distinct efficacy of KETO against tissue forms of L. donovani, we assumed that antimycotic azoles would also have a systemic action on Trypanosoma cruzi. We therefore investigated KETO, H 82 5338, -(2 -1,2,3,4-tetra-hydro-isoquinolin-6-yl)-ether, S 82 5183, 2-(imidazolyl-l-methyl)-2-(2,4-dichlorophenyl) 1,3 dioxolan 4 yl < 4-methoxy(morpholino-methylene-aniline), and ICI 153,066, 2-(1,2,4-triazol-l-yl)-l-(4-fluorophenyl)-l-(2,4-dichlorophenyl)-ethanol, in comparison with standard drugs in mice infected with T. cruzi (for details concerning materials and methods see Raether and Seidenath 1983).