Inhibition by dications of in vitro growth of Leishmania mojor and Leishmonia tropica:: Causative agents of Old World cutaneous leishmaniasis
Inhibition by dications of in vitro growth of Leishmania mojor and Leishmonia tropica:: Causative agents of Old World cutaneous leishmaniasis
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DOI：
10.1645/ge-1387.1
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发表时间：
2008-06-01
影响因子：
1.3
通讯作者：
Tidwell, Richard R.
中科院分区：
文献类型：
--
作者：
Rosypal, Alexa C.;Werbovetz, Karl A.;Tidwell, Richard R.
旧世界皮肤利什曼病是由感染利什曼原虫主要和热带利什曼原虫。喷他脒及其相关化合物具有广谱抗原虫活性。基于先前报道的这些化合物对相关生物体的功效，评价了喷他脒的18种结构类似物的体外抗利什曼原虫活性，使用喷他脒作为标准参比药物进行比较。检测了呋喃类似物和反脒化合物对L. major和L.热带前鞭毛体对两种利什曼原虫最有效的化合物是反脒系列。DB 745和DB 746对L. DB 745对L. major的活性最强。热带。这两种化合物对L.少校还测试了10种反向脒在纯无鞭毛体模型中抑制生长的能力。10种反向脒类似物中有9种在低于1 nM的浓度下具有活性。这些结果证明进一步研究双阳离子化合物作为潜在的治疗皮肤利什曼病的新药物。
Old World cutaneous leishmaniasis is caused by infection with Leishmania major and Leishmania tropica. Pentamidine and related dications exhibit broad spectrum antiprotozoal activity. Based on the previously reported efficacy of these compounds against related organisms, 18 structural analogs of pentamidine were evaluated for in vitro antileishmanial activity, using pentamidine as the standard reference drug for comparison. Furan analogs and reversed amidine compounds were examined for activity against L. major and L. tropica promastigotes. The most active compounds against both Leishmania species were in the reversed amidine series. DB745 and DB746 exhibited the highest activity against L. major and DB745 was the most active compound against L. tropica. Both of these compounds exhibited 50% inhibitory concentrations (IC50) below 1 nM for L. major. Ten reversed amidines were also tested for their ability to inhibit growth in an axenic amastigote model. Nine of 10 reversed amidine analogs were active at concentrations below 1 nM. These results justify further study of dicationic compounds as potential new agents for treating cutaneous leishmaniasis.