Department of Medical Parasitology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Exp Parasitol. 2013 Oct;135(2):208-16. doi: 10.1016/j.exppara.2013.07.004. Epub 2013 Jul 16.
This in silico and in vitro comparative study was designed to evaluate the effectiveness of some biurets (K1 to K8) and glucantime against Leishmania major and Leishmania infantum promastigotes. Overall, eight experimental ligands and glucantime were docked using AutoDock 4.3 program into the active sites of Leishmania major and Leishmania infantum pteridine reductase 1, which were modeled using homology modeling programs. The colorimetric MTT assay was used to find L. major and L. infantum promastigotes viability at different concentrations of biuret derivatives in a concentration and time-dependent manner and the obtained results were expressed as 50% and 90% of inhibitory concentration (IC₅₀ and IC₉₀). In silico method showed that out of eight experimental ligands, four compounds were more active on pteridine reductase 1. K3 was the most active against L. major promastigotes with an IC₅₀ of 6.8 μM and an IC₉₀ of 40.2 μM, whereas for L. infantum promastigotes was K8 with IC₅₀ of 7.8 μM. The phenylethyl derivative (K7) showed less toxicity (IC₅₀s>60 μM) in both Leishmania strains. Glucantime displayed less growth inhibition in concentration of about 20 μM. In silico and especially docking results in a recent study were in accordance with the in vitro activity of these compounds in presented study and compound K3, K2 and K8 showed reasonable levels of selectivity for the Leishmania pteridine reductase 1.
本计算机模拟和体外比较研究旨在评估一些双缩脲（K1 至 K8）和葡萄糖胺对利什曼原虫和婴儿利什曼原虫前鞭毛体的有效性。总体而言，使用 AutoDock 4.3 程序将八种实验配体和葡萄糖胺对接进入利什曼原虫和婴儿利什曼原虫蝶啶还原酶 1 的活性部位，使用同源建模程序对其进行建模。使用比色 MTT 测定法以浓度和时间依赖性方式在不同浓度的双缩脲衍生物下找到利什曼原虫和婴儿利什曼原虫前鞭毛体的活力，并将获得的结果表示为 50%和 90%的抑制浓度（IC₅₀和 IC₉₀）。计算机模拟方法表明，在八种实验配体中，有四种化合物对蝶啶还原酶 1 更具活性。K3 对利什曼原虫前鞭毛体的活性最强，IC₅₀为 6.8 μM，IC₉₀为 40.2 μM，而 K8 对婴儿利什曼原虫前鞭毛体的活性最强，IC₅₀为 7.8 μM。苯乙基衍生物（K7）在两种利什曼虫株中显示出较低的毒性（IC₅₀>60 μM）。葡萄糖胺在约 20 μM 的浓度下显示出较低的生长抑制作用。在最近的一项研究中，计算机模拟和特别是对接结果与本研究中这些化合物的体外活性一致，化合物 K3、K2 和 K8 对利什曼蝶啶还原酶 1 表现出合理的选择性。
