Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
J Antimicrob Chemother. 2011 Jul;66(7):1555-9. doi: 10.1093/jac/dkr158. Epub 2011 Apr 29.
This paper describes the antileishmanial properties of LQB-118, a new compound designed by molecular hybridization, orally active in Leishmania amazonensis-infected BALB/c mice.
In vitro antileishmanial activity was determined in L. amazonensis-infected macrophages. For in vivo studies, LQB-118 was administered intralesionally (15 μg/kg/day, five times a week), intraperitoneally (4.5 mg/kg/day, five times a week) or orally (4.5 mg/kg/day, five times a week) to L. amazonensis-infected BALB/c mice throughout experiments lasting 85 or 105 days. At the end of the experiments, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine were measured as toxicological parameters.
LQB-118 was active against intracellular amastigotes of L. amazonensis [50% inhibitory concentration (IC(50)) 1.4 μM] and significantly less so against macrophages (IC(50) 18.5 μM). LQB-118 administered intralesionally, intraperitoneally or orally was found to control both lesion and parasite growth in L. amazonensis-infected BALB/c mice, without altering serological markers of toxicity.
These results demonstrate that the molecular hybridization of a naphthoquinone core to pterocarpan yielded a novel antileishmanial compound that was locally and orally active in an experimental cutaneous leishmaniasis model.
本文描述了通过分子杂交设计的新化合物 LQB-118 的抗利什曼原虫特性，该化合物在感染利什曼原虫的 BALB/c 小鼠中具有口服活性。
在感染利什曼原虫的巨噬细胞中测定体外抗利什曼原虫活性。对于体内研究，将 LQB-118 经皮内（15μg/kg/天，每周 5 次）、腹腔内（4.5mg/kg/天，每周 5 次）或口服（4.5mg/kg/天，每周 5 次）给予感染利什曼原虫的 BALB/c 小鼠，实验持续 85 或 105 天。在实验结束时，作为毒理学参数测量血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和肌酐水平。
LQB-118 对利什曼原虫的细胞内无鞭毛体具有活性[50%抑制浓度（IC（50）1.4μM]，而对巨噬细胞的活性则明显较低（IC（50）18.5μM）。经皮内、腹腔内或口服给予 LQB-118 可控制感染利什曼原虫的 BALB/c 小鼠的病变和寄生虫生长，而不会改变毒性的血清学标志物。
这些结果表明，将萘醌核心与蝶豆素杂交得到了一种新型抗利什曼原虫化合物，该化合物在实验性皮肤利什曼病模型中具有局部和口服活性。
