Abstract
In many countries, the fruit of betel (Piper betle Linn) is traditionally used as medicine for treating malaria. It is a fatal disease, and existing medications are rapidly losing potency, necessitating the development of innovative pharmaceutics. The current study attempted to determine the compounds in the n-hexane fraction of betel fruit extract and investigate the potential inhibition of bioactive compounds against aspartic protease plasmepsin 1 (PDB ID: 3QS1) and plasmepsin 2 (PDB ID: 1LEE) of Plasmodium falciparum using a computational approach. The ethanol extract was fractionated into n-hexane and further analyzed using gas chromatography-mass spectrometry (GC-MS) to obtain information regarding the compounds contained in betel fruit. Each compound’s potential antimalarial activity was evaluated using AutoDock Vina and compared to artemisinin, an antimalarial drug. Molecular dynamics simulations (MDSs) were performed to evaluate the stability of the interaction between the ligand and receptors. Results detected 20 probable compounds in the n-hexane extract of betel fruit based on GC-MS analysis. The docking study revealed that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)- has the highest binding affinity for plasmepsin 1 and plasmepsin 2. The compound exhibits a similar interaction with artemisinin at the active site of the receptors. The compound does not violate Lipinski’s rules of five. It belongs to class 5 toxicity with an LD50 of 3000 mg/kg. MDS results showed stable interactions between the compound and the receptors. Our study concluded that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)- from betel fruit has the potential to be further investigated as a potential inhibitor of the aspartic protease plasmepsin 1 and plasmepsin 2 of Plasmodium falciparum.
Highlights
Malaria is an infectious disease that is very widespread worldwide, affecting 100 countries with tropical and subtropical climates
Due to drug resistance in the treatment of the disease with numerous medications, it is vital to look for promising medicinal plants in traditional antimalarial medicine that have been scientifically tested
This study suggests that AND has a favorable interaction with plasmepsin 1 and 2, based on their binding-free energy (BFE) values being greater than those of artemisinin
Summary
Malaria is an infectious disease that is very widespread worldwide, affecting 100 countries with tropical and subtropical climates. The disease is transmitted by mosquito vectors carrying unicellular parasites of the genus Plasmodium. Four species (P. falciparum, P. malariae, P. ovale, and P. vivax) have traditionally been recognized as natural causes of human infection, but the recent increase in malaria cases caused by Plasmodium knowlesi in Southeast Asia has led physicians to consider it the fifth parasite that causes malaria in humans [2]. The availability of safe, effective, practical, and economically affordable antimalarial drugs has improved, resulting in reduced mortality from the disease. Several drugs have been developed that inhibit or kill the asexual form of the parasite in human erythrocytes, such as quinine, chloroquine, pyrimethamine, sulfonamides, sulfones, and artemisinin derivatives. Parasites do not have an active site to bind chloroquine, so this drug cannot be concentrated in erythrocytes [6]. One of them is through utilizing a computer simulation approach
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