Uji farmakodinamik, drug-likeness, farmakokinetik dan interaksi senyawa aktif kayu ular (Strychnos lucida) sebagai inhibitor Plasmodium falciparum secara in silico
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Dede Rival Novian(1*)
Universitas Nusa Cendana
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Azra Zahrah Nadhirah Ikhwani(2)
Indonesian Institute of Sciences
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Aji Winarso(3)
Univesitas Nusa Cendana
(*) Corresponding Author
Keywords:
Drug-likeness, Molecular docking, PfLDH, Pharmacokinetic, Pharmacodynamic, snakewood’s active compound
Abstract
Snakewood’s active compounds have known to be potential as anti-plasmodium by the in-vitro study. However, the inhibition activity mechanism of snakewood active compounds against Plasmodium is not yet known. In this study, we determined the activity of snakewood’s active compounds by in-silico approach. Firstly, We identified the pharmacodynamic properties of snakewood’s active compounds, which are SA1, SA2, SA3, SA4, and SA5. Furthermore, drug-likeness and pharmacokinetic: absorption-distribution-metabolism-excretion (ADME) analyses were also carried out against snakewood’s active compounds to determine the most potential candidate for anti-Plasmodium falciparum drug. Molecular docking analyses using Plasmodium falciparum lactate dehydrogenase (PfLDH) enzyme against the active compounds were undertaken to observe their specific interactions. The result of molecular docking based on binding energy and inhibitory constant showed that SA3 (3-ethoxyacetophenone (C9H10O2)) active compound is the most potential inhibitor of PfLDH than others. It’s caused by the binding energy and inhibitory constant of SA3 lower than the other snakewood’s active compound. Therefore, SA3 can be a potential candidate for the anti-plasmodium agent.
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References
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[4] Krettli AU, Adebayo JO, Krettli LG. 2009. Testing of natural products and synthetic molecules aim-ing at new antimalarials. Curr Drug Targets. 10:261–270.
[5] Foley M, Tilley L 1998. Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. Pharmacol Ther. 79:55–87.
[6] Egan T, Ncokazi K. 2005. Quinoline antimalarials decrease the rate of beta-hematin formation. J In-org Biochem. 99:1532–1539.
[7] Read J, Wilkinson K, Tranter R, Sessions R, Brady R. 1999. Chloroquine binds in the cofactor bind-ing site of Plasmodium falciparum lactate dehydrogenase. J Biol Chem. 274:10213–10218.
[8] Ncokazi KK, Egan TJ. 2005. A colorimetric high-throughput beta-hematin inhibition screening as-say for use in the search for antimalarial compounds. Anal Biochem. 338:306–319.
[9] Menting J, Tilley L, Deady L, Ng K, Simpson R et al. 1997. The antimalarial drug, chloroquine, in-teracts with lactate dehydrogenase from Plasmodium falciparum. Mol Biochem Parasitol. 88:215–224.
[10] Balaban AT. 1982. Highly discriminating distance-based topological Index. Chem Phys Lett. 89:399-404.
[11] Kaushik D. Paliwal D, Kumar A. 2015. 2D QSAR and Molecular docking studies of chloroquine-thiazolidinone derivatives as potential pfLDH inhibitors of Plasmodium falciparum. International Journal of Pharmacology and Pharmaceutical Sciences. 2(5): 42-53
[12] Hughes JP, Rees S, Kalindjian SB, Philpott, KL. 2011. Principles of early drug discovery. Br. J. Pharmacol. 162:1239–1249.
[13] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 2012. Experimental and computational ap-proaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 64: 4–17.
[14]Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. 2000. The protein data bank. Nucleic Acids Res. 28: 235-242.
[15] Ferreira LG, dos Santos RN, Oliva G, Andricopulo AD. 2015. Molecular docking and Structure-Based Drug Design Strategies. Molecules. 20: 13384-13421.
[16] Singh IV dan Mishra S. 2018. Molecular docking Analysis of Pyrimethamine Derivatives with Plasmodium falciparum Dihydrofolate Reductase. J.Bioinformation. 14(5): 232-235.
[17] Fatmawaty, Hanafi M, Rosmalena, Prasasty VD. 2015. Skrining in silico potensi senyawa allicin dari allium sativum sebagai antiplasmodium. JKTI. 17(2): 175-184.
[18] Read JA, Wilkinson KW, Tranter R, Sessions RB, Brady RL. 1999. Chloroquine binds in the cofac-tor binding site of plasmodium falciparum lactate dehydrogenase. J Biol Chem. 274(15):10213-8.
[19]Syafii W, Sari RK, Cahyaningsih U, Anisah LN. 2016. Aktivitas Antimalaria Ekstrak Kayu Bidara Laut. J. Ilmu Teknol. Kayu Tropis. 14:1-10.
[20] Sadono A. 2011. Aktivitas Antioksidan dan Analisis Komposisi Senyawa Fenolik dari Pohon Bi-dara Laut (Strychnos ligustrina). Departemen Kimia Fakultas Matematika dan Ilmu Pengetahuan Alam. Institut Pertanian Bogor, Bogor.
[21] Molsoft LLC, version 2019. Drug-Likeness and molecular property prediction. Molsoft L.L.C. 11199 Sorrento Valley Road, S209 San Diego CA 92121. www.molsoft.com.
[22] ACD/Structure Elucidator, version 2018.1. 2019. Advanced Chemistry Development, Inc., Toronto, ON, Canada, www.acdlabs.com.
[23] Tanchuk VY, Tanin VO, Vovk AI, Poda G. 2015. A New Scoring Function for Molecular docking Based on AutoDock and AutoDock Vina. Curr Drug Discov Technol.
[24] kim S, et al. 2016. Pubchem Subtance and Compund databae. Nucleic Acid Res. 4;44 (D1): D1202-13.
[25] Marcus D Hanwell, Donald E Curtis, David C Lonie, Tim Vandermeersch, Eva Zurek and Geoffrey R Hutchison. 2012. “Avogadro: An advanced semantic chemical editor, visualization, and analysis plat-form” Journal of Cheminformatics 2012, 4:17.
[26] Negus ST and Banks ML. 2018. Pharmacokinetic – pharmacodinamic (PKDA) Analysis with Drug Dicrimination. Curr Top Behav Neurosci. 39: 245-259
[27] C.A. Lipinski. 2004. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies 1: 337–341.(2004)
[28] S. Shityakov, W. Neuhaus, T. Dandekar, C. Förster. 2013. Analysing molecular polar surface descriptors to predict blood-brain barrier permeation. Int. J. Comput. Biol. Drug Des. 6: 146-156.
[29] C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney. 2001. Experimental and computational ap-proaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46: 3–26.
[30] G. Borbely G, M. Huszar, A.Varga, K. Futosi, A. Mocsai. 2012. Optimization of important early ADME(T) parameters of NADPH oxidase-4 inhibitor molecules. Med Chem. 8: 174-181.
Published
2019-06-22
How to Cite
Novian, D., Ikhwani, A. Z., & Winarso, A. (2019). Uji farmakodinamik, drug-likeness, farmakokinetik dan interaksi senyawa aktif kayu ular (Strychnos lucida) sebagai inhibitor Plasmodium falciparum secara in silico. Jurnal Veteriner Nusantara, 2(1), 70-78. https://doi.org/10.35508/jvn.v2i1.1097
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