In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum
In vitro activity of dicationic compounds against a North American foxhound isolate of Leishmania infantum
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DOI：
10.1016/j.vetpar.2007.01.005
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发表时间：
2007-04-30
影响因子：
2.6
通讯作者：
Tidwell, Richard R.
中科院分区：
文献类型：
--
作者：
Rosypal, Alexa C.;Hall, James E.;Tidwell, Richard R.
由幼年利什曼原虫引起的犬利什曼病在北美猎狐犬种群中是地方性的。目前可用的化疗犬利什曼病不是完全有效的，复发是常见的治疗犬。喷他脒及其相关芳香二胺具有广谱抗原虫活性。以喷他脒为对照药，测定了35种芳香阳离子分子的体外抗利什曼原虫活性。研究了化合物对弗吉尼亚猎狐犬幼乳杆菌原鞭毛菌的抑菌活性。抗利什曼原虫活性最强的化合物为反相脒类化合物。化合物9的抑菌活性最高，IC50值为0.0042 μ M，而喷他脒的IC50值为14.2 μ M。9个化合物的抗利什曼原虫活性比对照药物至少高1000倍。本研究结果表明，一些与喷他脒相关的化合物值得进一步研究，作为治疗犬利什曼病的可能新药。(C) 2007 Elsevier B.V.版权所有
Canine leishmaniasis caused by Leishmania infantum is enzootic in the North American foxhound population. Currently available chemotherapy for canine leishmaniasis is not completely effective and relapses are common in treated dogs. Pentamidine and related aromatic diamidines possess broad spectrum antiprotozoal activity. The in vitro antileishmanial activities of 35 aromatic cationic molecules were determined, using pentamidine as the reference drug. The compounds were examined for activity against promastigotes of L. infantum isolated from a foxhound from Virginia. The compounds most active against Leishmania parasites were reversed amidines. Compound 9, a reversed amidine, exhibited the highest activity against L. infantum, with a 50% inhibitory concentration (IC50) of 0.0042 mu M compared with 14.2 mu M for pentamidine. Antileishmanial activities of nine compounds were at least 1000-fold higher relative to the reference drug. Results from this study indicate that several pentamidine-related compounds warrant further investigation as possible new agents for the treatment of canine leishmaniasis. (C) 2007 Elsevier B.V. All rights reserved.