{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:50:18Z","timestamp":1771473018338,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006261","name":"Taif University","doi-asserted-by":"publisher","award":["TURSP-2020\/310"],"award-info":[{"award-number":["TURSP-2020\/310"]}],"id":[{"id":"10.13039\/501100006261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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\u2019s 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ph14121285","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:46:58Z","timestamp":1639086418000},"page":"1285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2480-5420","authenticated-orcid":false,"family":"Fatimawali","sequence":"first","affiliation":[{"name":"Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, Indonesia"},{"name":"The University Center of Excellence for Biotechnology and Conservation of Wallacea, Institute for Research and Community Services, Sam Ratulangi University, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-7527","authenticated-orcid":false,"given":"Trina Ekawati","family":"Tallei","sequence":"additional","affiliation":[{"name":"The University Center of Excellence for Biotechnology and Conservation of Wallacea, Institute for Research and Community Services, Sam Ratulangi University, Manado 95115, Indonesia"},{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Billy Johnson","family":"Kepel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4326-6066","authenticated-orcid":false,"given":"Mohammed","family":"Alorabi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Science, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4357-4904","authenticated-orcid":false,"given":"Ahmed M.","family":"El-Shehawi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Science, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Widdhi","family":"Bodhi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sefren Geiner","family":"Tumilaar","sequence":"additional","affiliation":[{"name":"Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8146-1663","authenticated-orcid":false,"given":"Ismail","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-0495","authenticated-orcid":false,"given":"Gomaa","family":"Mostafa-Hedeab","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Health Sciences Research Unit, Medical College, Jouf University, Sakaka 72446, Saudi Arabia"},{"name":"Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni Suef 62521, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amany Abdel-Rahman","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-2272","authenticated-orcid":false,"given":"Talha Bin","family":"Emran","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ref_1","first-page":"129","article-title":"Aktivitas antimalaria (in vivo) kombinasi buah sirih (Piper betle L.), daun miyana (Plectranthus scutellarioides (L.) 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