Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach
In many countries, the fruit of betel (<i>Piper betle</i> 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 de...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/12/1285 |
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| author | Fatimawali Trina Ekawati Tallei Billy Johnson Kepel Mohammed Alorabi Ahmed M. El-Shehawi Widdhi Bodhi Sefren Geiner Tumilaar Ismail Celik Gomaa Mostafa-Hedeab Amany Abdel-Rahman Mohamed Talha Bin Emran |
| author_facet | Fatimawali Trina Ekawati Tallei Billy Johnson Kepel Mohammed Alorabi Ahmed M. El-Shehawi Widdhi Bodhi Sefren Geiner Tumilaar Ismail Celik Gomaa Mostafa-Hedeab Amany Abdel-Rahman Mohamed Talha Bin Emran |
| author_sort | Fatimawali |
| collection | DOAJ |
| description | In many countries, the fruit of betel (<i>Piper betle</i> 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 <i>Plasmodium falciparum</i> 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 LD<sub>50</sub> 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 <i>Plasmodium falciparum</i>. |
| first_indexed | 2024-03-10T03:20:18Z |
| format | Article |
| id | doaj.art-496930093b0d41478a42b18b8b9d9fd6 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:20:18Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-496930093b0d41478a42b18b8b9d9fd62023-11-23T10:03:35ZengMDPI AGPharmaceuticals1424-82472021-12-011412128510.3390/ph14121285Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational ApproachFatimawali0Trina Ekawati Tallei1Billy Johnson Kepel2Mohammed Alorabi3Ahmed M. El-Shehawi4Widdhi Bodhi5Sefren Geiner Tumilaar6Ismail Celik7Gomaa Mostafa-Hedeab8Amany Abdel-Rahman Mohamed9Talha Bin Emran10Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, IndonesiaThe University Center of Excellence for Biotechnology and Conservation of Wallacea, Institute for Research and Community Services, Sam Ratulangi University, Manado 95115, IndonesiaDepartment of Chemistry, Faculty of Medicine, Sam Ratulangi University, Manado 95115, IndonesiaDepartment of Biotechnology, College of Science, Taif University, Taif 21944, Saudi ArabiaDepartment of Biotechnology, College of Science, Taif University, Taif 21944, Saudi ArabiaDepartment of Chemistry, Faculty of Medicine, Sam Ratulangi University, Manado 95115, IndonesiaPharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, IndonesiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38039, TurkeyPharmacology Department, Health Sciences Research Unit, Medical College, Jouf University, Sakaka 72446, Saudi ArabiaDepartment of Forensic Medicine and Toxicology, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, BangladeshIn many countries, the fruit of betel (<i>Piper betle</i> 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 <i>Plasmodium falciparum</i> 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 LD<sub>50</sub> 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 <i>Plasmodium falciparum</i>.https://www.mdpi.com/1424-8247/14/12/1285<i>Piper betle</i>betel fruitmalariain silicoprotease inhibitorplasmepsin |
| spellingShingle | Fatimawali Trina Ekawati Tallei Billy Johnson Kepel Mohammed Alorabi Ahmed M. El-Shehawi Widdhi Bodhi Sefren Geiner Tumilaar Ismail Celik Gomaa Mostafa-Hedeab Amany Abdel-Rahman Mohamed Talha Bin Emran Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach Pharmaceuticals <i>Piper betle</i> betel fruit malaria in silico protease inhibitor plasmepsin |
| title | Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach |
| title_full | Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach |
| title_fullStr | Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach |
| title_full_unstemmed | Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach |
| title_short | Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach |
| title_sort | appraisal of bioactive compounds of betel fruit as antimalarial agents by targeting plasmepsin 1 and 2 a computational approach |
| topic | <i>Piper betle</i> betel fruit malaria in silico protease inhibitor plasmepsin |
| url | https://www.mdpi.com/1424-8247/14/12/1285 |
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