PHARMACOKINETIC PREDICTIONS AND MOLECULAR DYNAMIC ANALYSIS OF TERPENOID AND FLAVONOID COMPOUNDS FROM MIANA LEAVES (PLECTRANTHUS SCUTELLARIOIDES (L.) R. BR.) AS AN ANTIMALARIAL CANDIDATES ON PLASMEPSIN II RECEPTOR

Authors

  • AMI TJITRARESMI Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
  • KIRKA DWI APRIALI Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
  • KAMILA NURVIANITA Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
  • IDA MUSFIROH Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
  • MOELYONO MOEKTIWARDOYO Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
  • YASMIWAR SUSILAWATI Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022.v14s4.PP35

Keywords:

Miana, In silico, Malaria, Plasmepsin II

Abstract

Objective: This study aims to find antimalarial candidates from 32 terpenoids and three flavonoid compounds found in miana leaves in silico using plasmepsin protein as a receptor through docking simulations, molecular dynamics simulations, and pharmacokinetic predictions.

Methods: The research was conducted in silico through molecular docking simulation, molecular dynamic simulations, analysis of potential compounds using Lipinski’s rule, and prediction of ADMET based on ligands.

Results: The results showed isophytol had the best interaction with the plasmepsin II based on the low free binding energy (FBE) and led to hydrogen bonding with the plasmepsin II crucial amino acid, Asp34. Isophytol has the best result in molecular dynamic simulation. Based on pharmacokinetics predictions, toxicity, and Lipinski’s rule of five, most tested compounds, including isophytol, meet the criteria as a promising drug.

Conclusion: Isophytol from miana leaves with plasmepsin II protein has the best and most stable interaction based on the results of molecular dynamic simulation, so this compound was a candidate for antimalarial drugs.

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References

WHO. WHO guidelines for malaria. World Health Organization; 2021. http://apps.who.int/iris.

Rosenthal PJ. Antiprotozoal drugs. In: Katzung BG. editor Basic and Clinical Pharmacology. 14th ed. McGraw-Hill Education; 2017. p. 917-37.

Ippolito MM, Moser KA, Kabuya JBB, Cunningham C, Juliano JJ. Antimalarial drug resistance and implications for the WHO global technical strategy. Curr Epidemiol Rep. 2021;8(2):46-62. doi: 10.1007/s40471-021-00266-5, PMID 33747712.

Foley M, Tilley L. Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. Pharmacol Ther. 1998;79(1):55-87. doi: 10.1016/s0163-7258(98)00012-6, PMID 9719345.

Penna Coutinho J, Cortopassi WA, Oliveira AA, França TCC, Krettli AU. Antimalarial activity of potential inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies. PLOS ONE. 2011;6(7):e21237. doi: 10.1371/journal.pone.0021237, PMID 21779323.

Vennerstrom JL, Nuzum EO, Miller RE, Dorn A, Gerena L, Dande PA. 8-aminoquinolines active against blood-stage Plasmodium falciparum in vitro inhibit hematin polymerization. Antimicrob Agents Chemother. 1999;43(3):598-602. doi: 10.1128/AAC.43.3.598, PMID 10049273.

Meyers MJ, Goldberg DE. Recent advances in plasmepsin medicinal chemistry and implications for future antimalarial drug discovery efforts. Curr Top Med Chem. 2012;12(5):445-55. doi: 10.2174/156802612799362959, PMID 22242846.

Nasamu AS, Polino AJ, Istvan ES, Goldberg DE. Malaria parasite plasmepsins: more than just plain old degradative pepsins. J Biol Chem. 2020;295(25):8425-41. doi: 10.1074/jbc.REV120.009309, PMID 32366462.

Bhaumik P, Gustchina A, Wlodawer A. Structural studies of vacuolar plasmepsins. Biochim Biophys Acta. 2012;1824(1):207-23. doi: 10.1016/j.bbapap.2011.04.008, PMID 21540129.

Boss C, Richard Bildstein S, Weller T, Fischli W, Meyer S, Binkert C. Inhibitors of the Plasmodium falciparum parasite aspartic protease plasmepsin II as potential antimalarial agents. Curr Med Chem. 2003;10(11):883-907. doi: 10.2174/0929867033457674, PMID 12678679.

Cheuka PM, Dziwornu G, Okombo J, Chibale K. Plasmepsin inhibitors in antimalarial drug discovery: medicinal chemistry and target validation (2000 to present). J Med Chem. 2020;63(9):4445-67. doi: 10.1021/acs.jmedchem.9b01622, PMID 31913032.

Henderson JA, Shen J. Exploring the pH- and ligand-dependent flap dynamics of malarial plasmepsin II. J Chem Inf Model. 2022;62(1):150-8. doi: 10.1021/acs.jcim.1c01180, PMID 34964641.

Lisdawati V, Mutiatikum D, Alegantina SNY. Karakterisadi daun miana (Plectranthus scutellarioides (L.) BTH.) dan buah sirih (Piper betle L.) secara fisiko kimia dari ramuan lokal antimalaria daerah Sulawesi Utara. Media Health Res Dev. 2008;18.

Tjitraresmi A, Moektiwardoyo M, Susilawati Y, Shiono Y. Antimalarial activity of lamiaceae family plants. Syst Rev Pharm. 2020;11(7):324-33.

Cretton S, Saraux N, Monteillier A, Righi D, Marcourt L, Genta Jouve G. Anti-inflammatory and antiproliferative diterpenoids from Plectranthus scutellarioides. Phytochemistry. 2018;154:39-46. doi: 10.1016/j.phytochem.2018.06.012, PMID 29960256.

Kubinova R, Gazdova M, Hanakova Z, Jurkaninova S, Dall’Acqua S, Cvacka J. New diterpenoid glucoside and flavonoids from Plectranthus scutellarioides (L.) R. Br. S Afr J Bot. 2019;120:286-90. doi: 10.1016/j.sajb.2018.08.023.

Ito T, Rakainsa SK, Nisa K, Morita H. Three new abietane-type diterpenoids from the leaves of Indonesian Plectranthus scutellarioides. Fitoterapia. 2018;127:146-50. doi: 10.1016/j.fitote.2018.02.013, PMID 29447983.

Mustarichie R, Moektiwardoyo M, Dewi WA. Isolation, identification, and characteristic of essential oil of iler (Plectranthus scutellarioides (L.) R. Br leaves. J Pharm Sci Res. 2017;9(11):2218-23.

Dorr OS, Zimmermann BF, Kogler S, Mibus H. Influence of leaf temperature and blue light on the accumulation of rosmarinic acid and other phenolic compounds in Plectranthus scutellarioides (L.). Environ Exp Bot. 2019;167(June):103830. doi: 10.1016/j.envexpbot.2019.103830.

Moektiwardoyo M, Levita J, Sidiq SP, Ahmad K, Subarnas A, Java W. The determination of quercetin in Plectranthus scutellarioides (L.) R. Br. leaves extract and its in silico study on histamine H4 receptor penentuan kuersetin dari ekstrak metanol daun jawer. Majalah Farmasi Indones. 2011;22(3):191-6.

Ruswanto R, Mardianingrum R, Siswandono S, Kesuma D. Reverse docking, molecular docking, absorption, distribution, and toxicity prediction of artemisinin as an anti-diabetic candidate. Molekul. 2020;15(2):88. doi: 10.20884/1.jm.2020.15.2.579.

Chaniad P, Mungthin M, Payaka A, Viriyavejakul P, Punsawad C. Antimalarial properties and molecular docking analysis of compounds from Dioscorea bulbifera L. as new antimalarial agent candidates. BMC Complement Med Ther. 2021;21(1):144. doi: 10.1186/s12906-021-03317-y, PMID 34006257.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3-26. doi: 10.1016/s0169-409x(00)00129-0. PMID 11259830.

Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM. The amber biomolecular simulation programs. J Comput Chem. 2005;26(16):1668-88. doi: 10.1002/jcc.20290, PMID 16200636.

Mardianingrum R, Yusuf M, Hariono M, Mohd Gazzali A, Muchtaridi M. α-mangostin and its derivatives against estrogen receptor alpha. J Biomol Struct Dyn. 2022;40(6):2621-34. doi: 10.1080/07391102.2020.1841031, PMID 33155528.

Musfiroh I, Septiandi I, Megantara S, Tjitraresmi A, Muchtaridi. Interaction analysis of Asiatic acid and its derivatives to three isozyme of nitric oxide synthase (NOS) using molecular docking. Res J Chem Environ. 2019;23(12).

Shoichet BK, McGovern SL, Wei B, Irwin JJ. Lead discovery using molecular docking. Curr Opin Chem Biol. 2002;6(4):439-46. doi: 10.1016/s1367-5931(02)00339-3, PMID 12133718.

Subramanian G, Kitchen DB. Computational approaches for modeling human intestinal absorption and permeability. J Mol Model. 2006;12(5):577-89. doi: 10.1007/s00894-005-0065-z, PMID 16583199.

Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-61. doi: 10.1002/jcc.21334, PMID 19499576.

Malau ND. Antimalarial activity in plasmepsin II inhibitors using molecular docking. Int J Prog Sciences Technol. 2021;7(1):111-20.

Chaturvedi P, Raina V, Solanki PS, Saxena VL. In silico prediction of the anti-plasmodial activity of spices: targeting malarial proteases. J Clin Diagn Res. 2019;13(8):1-6. doi: 10.7860/JCDR/2019/34534.13035.

Ramachandran B, Kesavan S, Rajkumar T. Molecular modeling and docking of small molecule inhibitors against NEK2. Bio information. 2016;12(2):62-8. doi: 10.6026/97320630012062, PMID 28104962.

Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004;1(4):337-41. doi: 10.1016/j.ddtec.2004.11.007, PMID 24981612.

Cheng F, Li W, Liu G, Tang Y. In silico ADMET prediction: recent advances, current challenges and future trends. Curr Top Med Chem. 2013;13(11):1273-89. doi: 10.2174/ 15680266113139990033, PMID 23675935.

Purwaniati P. Molecular docking study on COVID-19 drug activity of N-(2-phenylethyl) methanesulfonamide derivatives as main protease inhibitor. Addawaa J Pharm Sci. 2020;3(1). doi: 10.24252/djps.v3i1.13945.

Published

26-11-2022

How to Cite

TJITRARESMI, A., APRIALI, K. D., NURVIANITA, K., MUSFIROH, I., MOEKTIWARDOYO, M., & SUSILAWATI, Y. (2022). PHARMACOKINETIC PREDICTIONS AND MOLECULAR DYNAMIC ANALYSIS OF TERPENOID AND FLAVONOID COMPOUNDS FROM MIANA LEAVES (PLECTRANTHUS SCUTELLARIOIDES (L.) R. BR.) AS AN ANTIMALARIAL CANDIDATES ON PLASMEPSIN II RECEPTOR. International Journal of Applied Pharmaceutics, 14(4), 142–150. https://doi.org/10.22159/ijap.2022.v14s4.PP35

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