Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, 65145 Malang, East Java, Indonesia.
Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Universitas Brawijaya, Malang 65141, East Java, Indonesia.
Biomed Res Int. 2020 Jan 9;2020:6135696. doi: 10.1155/2020/6135696. eCollection 2020.
Malaria is one of the life-threatening diseases in the world. The spread of resistance to antimalarial drugs is a major challenge, and resistance to artemisinin has been reported in the Southeast Asian region. In the previous study, the active compound of subsp. Hygroscopicus (. ), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the parasite, identifying and analyzing the effectiveness of compounds contained in . through instrumentation of liquid chromatography/mass spectrometry (LC/MS) and in silico studies were very useful. This study aimed at identifying other derivative compounds from . and screening the antimalarial activity of the compound by assessing the binding affinity, pharmacokinetic profile, and bond interaction. The derivative compounds were identified using LC/MS. Protein targets for derivative compounds were found through literature studies, and the results of identification of compounds and protein targets were reconstructed into three-dimensional models. Prediction of pharmacokinetic profiles was carried out using Swiss ADME. Screening of protein targets for the derivative compound was carried out using the reverse molecular docking method. Analyzing bond interaction was done by LigPlot. One compound from . , i.e., 6,7-dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione, was successfully identified using LC/MS. This compound was an isoquinoline derivative compound. Through literature studies with inclusion criteria, thirteen protein targets were obtained for reverse molecular docking. This isoquinoline derivative had the potential to bind to each protein target. The pharmacokinetic profile showed that this compound had the drug-likeness criteria. . 6,7-Dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione has antimalarial activity as shown by reverse molecular docking studies and pharmacokinetic profiles. The best inhibitory ability of compounds based on bond affinity is with adenylosuccinate synthetase.
疟疾是世界上危及生命的疾病之一。抗疟药物耐药性的传播是一个主要挑战，并且在东南亚地区已经报告了对青蒿素的耐药性。在之前的研究中，已经表明 Hygroscopicus 的活性化合物（. ），埃坡霉素具有抗疟作用。为了进一步分析其他活性化合物对寄生虫的影响，通过液相色谱/质谱（LC/MS）仪器和计算机模拟研究鉴定和分析 Hygroscopicus 中包含的化合物的有效性非常有用。本研究旨在从 Hygroscopicus 中鉴定其他衍生化合物，并通过评估结合亲和力、药代动力学特征和键相互作用来筛选该化合物的抗疟活性。使用 LC/MS 鉴定衍生化合物。通过文献研究发现衍生化合物的蛋白质靶标，并将化合物和蛋白质靶标的鉴定结果重建为三维模型。使用 Swiss ADME 进行药代动力学特征预测。使用反向分子对接方法筛选衍生化合物的蛋白质靶标。通过 LigPlot 分析键相互作用。使用 LC/MS 成功鉴定出 Hygroscopicus 中的一种化合物，即 6,7-二硝基-2-[1,2,4]三唑-4-基-苯并[de]异喹啉-1,3-二酮。该化合物是一种异喹啉衍生物。通过纳入标准的文献研究，获得了 13 个用于反向分子对接的蛋白质靶标。这种异喹啉衍生物有可能与每个蛋白质靶标结合。药代动力学特征表明该化合物具有药物特征。通过反向分子对接研究和药代动力学特征，6,7-二硝基-2-[1,2,4]三唑-4-基-苯并[de]异喹啉-1,3-二酮具有抗疟活性。基于键亲和力的化合物的最佳抑制能力是与腺嘌呤核苷酸合成酶。
