Abstract
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 Streptomyces hygroscopicus subsp. Hygroscopicus (S. hygroscopicus), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the Plasmodium parasite, identifying and analyzing the effectiveness of compounds contained in S. hygroscopicus 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 S. hygroscopicus 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 S. hygroscopicus, 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. Conclusion. 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.
Highlights
Malaria is one of the top ten deadly diseases in the world and has been a global health threat for centuries [1]
We report the newest antimalarial agent, the isoquinoline derivative from S. hygroscopicus through in silico approach
Visualization of Interaction. e stronger binding affinities between the derivative compound and protein targets compared to the native ligands were visualized using LigPlot 1.4.5. e visualization is used to assess whether the residues that formed are consistent with the score of binding affinities [14]. e derivative compound is predicted to have strong bond to the targets if it is capable of binding strongly through hydrogen bonds with the same amino acid residue compared to the control ligand [45]
Summary
Malaria is one of the top ten deadly diseases in the world and has been a global health threat for centuries [1]. Analysis of eponemycin analogues from the metabolite extract of S. hygroscopicus has been carried out by another research by Fitri et al [11] who used the thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) methods and stated that the active fraction of S. hygroscopicus has the potential to be a candidate for new antimalarial drugs and can cause stress on Plasmodium berghei [11]. Reverse docking is usually used to find out new targets of a drug whose mechanism of action is known or natural products have unknown therapeutic effects [14]. Reverse docking in this study can be used to determine and assess the potential of the active compound of S. hygroscopicus as an antimalarial agent through its association with protein targets in Plasmodium parasite. We report the newest antimalarial agent, the isoquinoline derivative from S. hygroscopicus through in silico approach
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