LC-MS Chemical Profiling, In Silico Docking Studies to Unravel the Therapeutic Potential of Streptomyces hygroscopicus as a Source of Antimalarial Bioactive Compounds
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Abstract
Malaria is a disease transmitted through the bite of female Anopheles mosquitoes carrying Plasmodium parasite. The resistance of the Plasmodium parasite against antimalarial drugs is a critical health concern necessitating the development of novel antimalarial treatments. Previous investigations reported that the crude extract of Streptomyces hygroscopicus Subsp. Hygroscopicus (S. hygroscopicus) possessed antimalarial properties, with in vitro assays confirming the ability to inhibit Plasmodium growth. Therefore, this research aimed to identify derivative compounds from S. hygroscopicus using Liquid Chromatography-Mass Spectrometry (LC-MS) and assess antimalarial activity by examining the binding site, pharmacokinetic profiles, and binding interactions through in silico analysis. In silico reverse molecular docking study was conducted with target proteins including Plasmodium falciparum malarial M1 aminopeptidase (PfA-M1), Plasmodium falciparum chloroquine resistance transporter (PfCRT), and falcipain-2 protease obtained from Protein Data Bank (PDB) and active compound ligands retrieved from PubChem. In addition, the analysis of pharmacokinetic profiles and bond interactions was performed using the SwissADME web tool and LigPlot software, respectively. The LC-MS analysis results showed that four compounds including dibenzyl amine, sedanolide, levalbuterol, and dibutyl phthalate with high retention times met the drug similarity criteria and had binding affinity values comparable to control ligands of the respective target proteins. The four compounds may have antimalarial activity due to the formation of hydrogen and hydrophobic bonds identical to those found between the target proteins and control ligands. Specifically, dibenzyl amine expressed the highest binding affinity across all target proteins, suggesting it as a potential antimalarial candidate.
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