Laboratorio de Biología Celular de Parásitos, Instituto de Biología Experimental, Universidad Central de Venezuela, Caracas, Venezuela.
Exp Parasitol. 2010 Dec;126(4):557-63. doi: 10.1016/j.exppara.2010.06.002. Epub 2010 Jun 8.
In this work, we have found an antiproliferative effect on Leishmania sp. promastigotes and axenic amastigotes by the human immunodeficiency virus (HIV) aspartyl-proteinase inhibitors, Ac-Leu-Val-Phenylalaninal, Saquinavir mesylate and Nelfinavir, the latter two being used as part of antiretroviral therapy. This effect appears to be the result of cell division blockage. In addition, these drugs induced in culture a decrease in the percentage of co-infected HIV/Leishmania monocytes and amastigotes of Leishmania per macrophage. The finding of a dose-dependent inhibition of Leishmania promastigotes aspartyl-proteinase activity by these drugs allows us to propose this activity as the drug parasite target. A direct action of these HIV aspartyl-proteinase inhibitors on the parasite, would be correlated with the effect that highly active antiretroviral therapy have had in the decrease of HIV/Leishmania coinfection, opening an interesting perspective for new drugs research development based on this novel parasite proteinase family.
在这项工作中，我们发现人类免疫缺陷病毒（HIV）天冬氨酰蛋白酶抑制剂 Ac-Leu-Val-Phenylalaninal、Saquinavir 甲磺酸盐和 Nelfinavir 对 Leishmania sp. 前鞭毛体和无鞭毛体有抗增殖作用，后两者被用作抗逆转录病毒治疗的一部分。这种作用似乎是细胞分裂受阻的结果。此外，这些药物在培养中诱导感染 HIV/利什曼原虫的单核细胞和巨噬细胞内利什曼原虫无鞭毛体的百分比降低。这些药物对 Leishmania 前鞭毛体天冬氨酰蛋白酶活性的剂量依赖性抑制作用的发现，使我们能够提出将这种活性作为药物寄生虫靶标。这些 HIV 天冬氨酰蛋白酶抑制剂对寄生虫的直接作用，可能与高效抗逆转录病毒疗法在降低 HIV/利什曼原虫共感染方面的效果有关，为基于这种新型寄生虫蛋白酶家族的新药研究开发开辟了一个有趣的前景。
