DOI: https://doi.org/10.14710/jksa.24.3.101-107

Molecular Docking of Red Betel (Piper crocatum Ruiz & Pav) Bioactive Compounds as HMG-CoA Reductase Inhibitor

Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, 16680, Indonesia

Received: 19 Jan 2021; Revised: 14 Mar 2021; Accepted: 22 Mar 2021; Published: 31 Mar 2021.
Open Access Copyright 2021 Jurnal Kimia Sains dan Aplikasi under http://creativecommons.org/licenses/by-sa/4.0.

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Abstract

Cholesterol plaque buildup in artery walls occurs due to oxidation of Low-Density Lipoprotein (LDL) molecules by free radicals, which are a risk factor for coronary heart disease. Piper crocatum contains active compounds that can act as HMG-CoA reductase inhibitors, such as flavonoids, alkaloids, polyphenols, tannins, and essential oils. This study aimed to predict the potential of Piper crocatum extract and fraction compounds as HMG-CoA reductase inhibitors by investigating the ligand affinity to the HMG-CoA reductase enzyme. Ligand and receptor preparation was conducted using BIOVIA Discovery Studio Visualizer v16.1.0.15350 and AutoDock Tools v.1.5.6. Molecular docking used AutoDock Vina, while ligand visualization and receptor binding used PyMOL(TM) 1.7.4.5.Edu. The receptor used was HMG-CoA reductase (PDB code: 1HWK) with atorvastatin as a control ligand. Catechin, schisandrin B, and CHEMBL216163 had the highest inhibition with affinity energies of -7.9 kcal/mol, -8.2 kcal/mol, -8.3 kcal/mol, respectively. Amino acid residues that played a role in ligand and receptor interactions were Ser684, Asp690, Lys691, Lys692.

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Keywords: bioactive compounds; HMG-CoA reductase; molecular docking; Piper crocatum
Funding: Institut Pertanian Bogor

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Section: Research Articles
Language : EN
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  1. P. McGowan Mary, Hamed Hosseini Dehkordi Seyed, M. Moriarty Patrick, P. Barton Duell, Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia, Journal of the American Heart Association, 8, 24, (2019), e013225 https://doi.org/10.1161/JAHA.119.013225
  2. World Heart Federation, Global Heart Special Issue - The 2000-2016 WHF Global Atlas of CVD, World Heart Federation, 2018
  3. Badan Penelitian dan Pengembangan Kesehatan (LPB), Laporan Nasional Riskedas 2018, Badan Penelitian dan Pengembangan Kesehatan (LPB), Jakarta, 2018
  4. Jill Jin, Testing for “Silent” Coronary Heart Disease, JAMA, 312, 8, (2014), 858-858 https://doi.org/10.1001/jama.2014.9191
  5. Jonathan A. Tobert, Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors, Nature Reviews Drug Discovery, 2, 7, (2003), 517-526 https://doi.org/10.1038/nrd1112
  6. Herryawan Herryawan, Indah Puti Rahmayani Sabirin, The effectiveness of red betel leaf (Piper crocatum) extract against periodontal pathogens, Bali Medical Journal, 7, 3, (2018), 732-735 http://doi.org/10.15562/bmj.v7i3.1173
  7. Gunasekaran Baskaran, Shamala Salvamani, Siti Aqlima Ahmad, Noor Azmi Shaharuddin, Parveen Devi Pattiram, Mohd Yunus Shukor, HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella alba leaf extract as a treatment for hypercholesterolemia, Drug design, development and therapy, 9, (2015), 509-517 https://doi.org/10.2147/DDDT.S75056
  8. Mega Safithri Hasibuan, Sedarnawati Yasni, Maria Bintang, Anna Setiadi Ranti, Antihyperglicemic activity of Piper crocotum leaves and cinnamomum burmanii bark mixture extract in streptozotocin-induced diabetic rats, Journal of Mathematical and Fundamental Sciences, 48, 2, (2016), 178-191 https://doi.org/10.5614/j.math.fund.sci.2016.48.2.8
  9. Sonia Sharma, Adarsh Pal Vig, Evaluation of in vitro antioxidant properties of methanol and aqueous extracts of Parkinsonia aculeata L. leaves, The Scientific World Journal, 2013, (2013), Article ID 604865 https://doi.org/10.1155/2013/604865
  10. Saru Noliqo Rangkuti, Lely Sari Lubis, Uji Efektivitas Nanopartikel Daun Sirih Merah (Piper Crocatum Ruiz & Pav.) sebagai Penurun Kadar Kolesterol Serum Darah Marmot (Cavia Cobaya), Jurnal Farmagazine, 5, 1, (2018), 31-39 http://dx.doi.org/10.47653/farm.v5i1.92
  11. J. Mercy Jasmine, R. Vanaja, In silico analysis of phytochemical compounds for optimizing the inhibitors of HMG CoA reductase, Journal of Applied Pharmaceutical Science, 3, 9, (2013), 43-47 http://doi.org/10.7324/JAPS.2013.3908
  12. Adelia Adrianne Tapiory, Kadita Octavia Pertiwi, Khalisa Fadilla, Davy Reyhanditya, Fatchiyah Fatchiyah, In-Silico Analysis of Methoxyl Pectin Compounds from Banana Peels as HMG-CoA Reductase Inhibitor Complexes, Journal of Smart Bioprospecting and Technology, 1, 2, (2020), 46-50 https://doi.org/10.21776/ub.jsmartech.2020.001.02.5
  13. Subramanian Suganya, Balaji Nandagopal, Anand Anbarasu, Natural Inhibitors of HMG-CoA Reductase—An Insilico Approach Through Molecular Docking and Simulation Studies, Journal of Cellular Biochemistry, 118, 1, (2017), 52-57 https://doi.org/10.1002/jcb.25608
  14. M Safithri, A Kurniawati, Formula of Piper crocatum, Cinnamomum burmanii, and Zingiber officinale extracts as a functional beverage for diabetics, International Food Research Journal, 23, 3, (2016), 1123-1130
  15. Mai Anugrahwati, Tuti Purwaningsih, Rustina, J. A. Manggalarini, N. B. Alnavis, D. N. Wulandari, H. D. Pranowo, Extraction of Ethanolic Extract of Red Betel Leaves and Its Cytotoxicity Test on HeLa Cells, Procedia Engineering, 148, (2016), 1402-1407 https://doi.org/10.1016/j.proeng.2016.06.569
  16. Heni Sundari, M. Hatta Prabowo, Farida Juliantina Rachmawaty, Hady Anshory Tamhid, Standardization of leaf extract of red betel(Piper crocatum) leaves using ethanol, Jurnal Kedokteran dan Kesehatan Indonesia, 7, 1, (2016), 3-9 https://doi.org/10.20885/JKKI.Vol7.Iss1.art2
  17. Fitri Ramadani, Aktivitas antioksidan, total tanin ekstrak dan fraksi daun sirih merah (Piper crocatum) dan identifikasi dengan LC-MS, undergraduate thesis, Department of Biochemistry, IPB University, Bogor, 2018
  18. Ida Ayu Indah Wedaswari, Aktivitas Ekstrak Etanol dan Fraksi Daun Sirih Merah (Piper crocatum) dengan Metode Rancimat dan Identifikasi dengan LC-MS, undergraduate thesis, Department of Biochemistry, IPB University, Bogor, 2018
  19. Peter Juma Ochieng, Tony Sumaryada, Daniel Okun, Molecular Docking and Pharmacokinetic Prediction of Herbal Derivatives as Maltase-Glucoamylase Inhibitor, Asian Journal of Pharmaceutical and Clinical Research, 10, 9, (2017), 392-398 https://doi.org/10.22159/ajpcr.2017.v10i9.19337
  20. Oleg Trott, Arthur J. Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, Journal of Computational Chemistry, 31, 2, (2010), 455-461 https://doi.org/10.1002/jcc.21334
  21. Garrett M. Morris, Ruth Huey, William Lindstrom, Michel F. Sanner, Richard K. Belew, David S. Goodsell, Arthur J. Olson, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, Journal of Computational Chemistry, 30, 16, (2009), 2785-2791 https://doi.org/10.1002/jcc.21256
  22. Daniel Seeliger, Bert L. de Groot, Ligand docking and binding site analysis with PyMOL and Autodock/Vina, Journal of Computer-Aided Molecular Design, 24, 5, (2010), 417-422 https://doi.org/10.1007/s10822-010-9352-6
  23. Endang Lukitaningsih, Anny A. Mustikawaty, Ari Sudarmanto, Homology Modeling and Molecular Docking of Active Compounds from Bengkoang (Pachyrrhizus erosus) as Tyrosinase Inhibitor in Homo sapiens, Jurnal Ilmu Kefarmasian Indonesia, 11, 2, (2013), 134-141
  24. Xiao Li, Lei Chen, Feixiong Cheng, Zengrui Wu, Hanping Bian, Congying Xu, Weihua Li, Guixia Liu, Xu Shen, Yun Tang, In Silico Prediction of Chemical Acute Oral Toxicity Using Multi-Classification Methods, Journal of Chemical Information and Modeling, 54, 4, (2014), 1061-1069 https://doi.org/10.1021/ci5000467
  25. Diana S. Gesto, Carlos M. S. Pereira, Nuno M. F. S. Cerqueira, Sérgio F. Sousa, An Atomic-Level Perspective of HMG-CoA-Reductase: The Target Enzyme to Treat Hypercholesterolemia, Molecules, 25, 17, (2020), 3891 https://doi.org/10.3390/molecules25173891
  26. Eva S. Istvan, Johann Deisenhofer, Structural Mechanism for Statin Inhibition of HMG-CoA Reductase, Science, 292, 5519, (2001), 1160 https://doi.org/10.1126/science.1059344
  27. Eva S. Istvan, Johann Deisenhofer, The structure of the catalytic portion of human HMG-CoA reductase, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1529, 1, (2000), 9-18 https://doi.org/10.1016/S1388-1981(00)00134-7
  28. László Ferencz, Daniela Lucia Muntean, Possible substitutes for paracetamol: the results of a comprehensive screening based on structural similarity and docking simulation on the surface of enzymes, Farmacia, 63, (2015), 422-428
  29. Hari Purnomo, Kimia Komputasi untuk Farmasi dan Ilmu Terkait; Uji In Silico Senyawa Antikanker, Pustaka Pelajar, Yogyakarta, 2013
  30. Christopher Llynard D. Ortiz, Gladys C. Completo, Ruel C. Nacario, Ricky B. Nellas, Potential Inhibitors of Galactofuranosyltransferase 2 (GlfT2): Molecular Docking, 3D-QSAR, and In Silico ADMETox Studies, Scientific Reports, 9, 1, (2019), 17096 https://doi.org/10.1038/s41598-019-52764-8

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