Inhibitory Effect of Active Substances of Lollyfish (Holothuria atra) Against the Development of Plasmodium falciparum Based on In Silico Study

*Felly Moelyadi orcid  -  Hang Tuah University, Indonesia
Prawesty Diah Utami  -  Hang Tuah University, Indonesia
Irmawati M. Dikman  -  Hang Tuah University, Indonesia
Received: 12 Jul 2020; Revised: 25 Aug 2020; Accepted: 7 Oct 2020; Published: 24 Nov 2020; Available online: 24 Nov 2020.
DOI: https://doi.org/10.14710/ik.ijms.25.4.135-142 View
Absorption, Distribution, Metabolism, Excretion and Toxicity Class of Substances in Lollyfish (Holothuria atra)
Subject Holothuria atra; lollyfish; toxicity
Type Research Results
  Download (925KB)    Indexing metadata
Open Access License URL: http://creativecommons.org/licenses/by-nc-sa/4.0

Citation Format:
Abstract

The high level of artemisinin resistance as the antimalarial drug makes the active substances found of lollyfish (Holothuria atra) become a very useful discovery as a new antimalarial drug. The purpose of this research is to find out the inhibitory effect of the active substances of lollyfish against the development of Plasmodium falciparum with in silico method. This is a one-shot experimental study research. Based on the test of potentially active substances of lollyfish through PubChem (https://pubchem.ncbi.nlm.nih.gov/), there are pyrogallol and catechin that have potential as the antimalarial drug. Pyrogallol, chlorogenic acid, catechin dan ascorbic acid have indirect inhibition to P. falciparum Orotidine 5-Monophosphate Decarboxylase (PfOMPDC) through carbon dioxide (CO2) and it is visualized by STITCH DB Version 5.0 (http://stitch.embl.de/). The binding affinity score of catechin, obtained from molecular docking, is higher than other substances and artemisinin. The Physicochemical and pharmacokinetic activity of the substance was predicted through SWISS ADME (http://www.swissadme.ch/index.php), while the toxicity was predicted through Pro-Tox (http://tox.charite.de/protox_II/). Catechin is a substance in lollyfish that is the safest because its lowest toxicity and very effective to be used as the antimalarial drug because of its high lethal dose 50 (LD50). Therefore, active substances in lollyfish have inhibitory effects against the development of P. falciparum based on in silico study.

Note: This article has supplementary file(s).

Keywords: in silico; lollyfish; malaria; PfOMPDC
Funding: Hang Tuah University; Laboratorium Biomolekuler & Bioinformatika INBIO

Article Metrics:

  1. Abdulah, R., Suradji, E.W., Subarnas, A., Supratman, U., Sugijanto, M., Diantini, A., Lestari, K., Barliana, M.I., Kawazu, S. & Koyama, H. 2017. Catechin isolated from Garcinia celebica leaves inhibit Plasmodium falciparum growth through the induction of oxidative stress, Pharmacogn. Mag., 13(2):301-305. https://doi.org/10.4103/pm.pm_571_16
  2. Al-Jaber, H.I., Mosleh, I.M., Mallouh, A., Abu Salim, O.M. & Abu Zarga, M.H. 2010. Chemical constituents of Osyris alba and their antiparasitic activities, J. Asian Nat. Prod. Res., 12(9):814-820. https://doi.org/10.1080/10286020.2010.502892
  3. Arsianti, A., Astuty, H., Fadilah, Bahtiar, A., Tanimoto, H. & Kakiuchi, K. 2017. Design and screening of gallic acid derivatives as inhibitors of malarial dihydrofolate reductase by in silico docking, Asian J. Pharm. Clin. Res., 10(2):330-334. https://doi.org/10.22159/ajpcr.2017.v10i2.15712
  4. Banerjee, P., Eckert, A.O., Schrey, A.K. & Preissner, R. 2018. ProTox-II: A webserver for the prediction of toxicity of chemicals, Nucleic Acids Res., 46(W1):W257-W263
  5. https://doi.org/10.1093/nar/gky318
  6. Benet, L.Z., Hosey, C.M., Ursu, O. & Oprea, T.I. 2016. BDDCS, the Rule of 5 and drugability, Adv. Drug Deliv. Rev., 101:89-98. https://doi.org/10.1016/j.addr.2016.05.007
  7. Daina, A., Michielin, O. & Zoete, V. 2017. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7(1):42717. https://doi.org/10.1038/srep42717
  8. Erhirhie, E.O., Ihekwereme, C.P. & Ilodigwe, E.E. 2018. Advances in acute toxicity testing: Strengths, weaknesses and regulatory acceptance, Interdiscip. Toxicol. 11(1):5-12
  9. https://doi.org/10.2478/intox-2018-0001
  10. Fairhurst, R.M. & Dondorp, A.M. 2016. Artemisinin-Resistant Plasmodium falciparum Malaria, Microbiol. Spectr., 4(3): 455-467. https://doi.org/10.1128/microbiolspec.EI10-0013-2016
  11. Filimonov, D.A., Druzhilovskiy, D.S., Lagunin, A.A., Gloriozova, T.A., Rudik, A.V., Dmitriev, A.V., Pogodin, P.V. & Poroikov, V.V. 2018. Computer-aided prediction of biological activity spectra for chemical compounds: opportunities and limitation', Biomed. Chemi. Res. Methods, 1(1):1-21. https://doi.org/10.18097/BMCRM00004
  12. Krungkrai, S.R. & Krungkrai, J. 2016. Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target, Asian Pacific J. Trop. Med., 9(6):525-534. https://doi.org/10.1016/j.apjtm.2016.04.012
  13. Li, W. & Wang, C. 2015. Biodegradation of gallic acid to prepare pyrogallol by Enterobacter aerogenes through substrate induction, BioResources, 10(2):3027-3044. https://doi.org/10.15376/biores.10.2.3027-3044
  14. Lima, V.N., Oliveira-Tintino, C.D.M., Santos, E.S., Morais, L.P., Tintino, S.R., Freitas, T.S., Geraldo, Y.S., Pereira, R.L. S., Cruz, R.P., Menezes, I.R.A. & Coutinho, H.D.M. 2016. Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol, Microb. Pathog., 99:56-61. https://doi.org/10.1016/j.micpath.2016.08.004
  15. Lutgen, P. 2018. Tannins in Artemisia: the hidden treasure of prophylaxis, Pharm. Pharmacol. Int. J., 6(3):176-181. https://doi.org/10.15406/ppij.2018.06.00173
  16. Maier, A.G., Matuschewski, K., Zhang, M. & Rug, M. 2019. Plasmodium falciparum, Trends Parasitol. 35(6):481-482. https://doi.org/10.1016/j.pt.2018.11.010
  17. Meng, X.Y., Zhang, H.X., Mezei, M. & Cui, M. 2012. Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery, Curr. Comput. Aided Drug Des., 7(2):146-157. https://doi.org/10.2174/157340911795677602
  18. Muthusamy, M., Hwang, J.E., Kim, S.H., Kim, J.A., Jeong, M.J., Park, H.C. & Lee, S.I. 2019. Elevated carbon dioxide significantly improves ascorbic acid content, antioxidative properties and restricted biomass production in cruciferous vegetable seedlings, Plant Biotechnol. Rep., 13(3):293-304. https://doi.org/10.1007/s11816-019-00542-3
  19. Nishanth, G. & Schlüter, D. 2019. Blood-Brain Barrier in Cerebral Malaria: Pathogenesis and Therapeutic Intervention, Trends Parasitol., 35(7):516-528. https://doi.org/10.1016/j.pt.2019.04.010
  20. Pangestuti, R. & Arifin, Z. 2018. Medicinal and health benefit effects of functional sea cucumbers, J. Tradit Complement. Med., 8(3):341-351. https://doi.org/10.1016/j.jtcme.2017.06.007
  21. Putra, T.R.I. 2011. Malaria dan Permasalahannya, J. Kedok. Syiah Kuala, 11(2):103-114
  22. Raj, J., Chandra, M., Dogra, T.D., Pahuja, M. & Raina, A. 2013. Determination of median lethal dose of combination of endosulfan and cypermethrin in wistar rat, Toxicol. Int., 20(1):1-5. doi: 10.4103/0971-6580.111531
  23. https://doi.org/10.4103/0971-6580.111531
  24. Richard, J.P., Amyes, T.L. & Reyes, A.C. 2018. Orotidine 5′-Monophosphate Decarboxylase: Probing the Limits of the Possible for Enzyme Catalysis, Acc. Chem. Res., 51(4):960-969. https://doi.org/10.1021/acs.accounts.8b00059
  25. Stipanuk, M. & Caudill, M. 2012. Biochemical, Physiological, and Molecular Aspects of Human Nutrition 3rd Edition, Med. Sci. Sports Exerc. ELSEVIER, p. 448
  26. Szklarczyk, D., Santos, A., Von Mering, C., Jensen, L.J., Bork, P. & Kuhn, M. 2016. STITCH 5: Augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res., 44(D1):380-384
  27. https://doi.org/10.1093/nar/gkv1277
  28. Wadood, A., Ahmed, N., Shah, L., Ahmad, A., Hassan, H. & Shams, S. 2013. In-silico drug design: An approach which revolutionarised the drug discovery process, Drug Design and Deliv., 1(1):1-4
  29. https://doi.org/10.13172/2054-4057-1-1-1119
  30. WHO (2019) World Malaria Report 2019, World Health Organization. Available at: https://www.who.int/publications-detail-redirect/world-malaria-report-2019. Acessed 3 March 2020
  31. World Health Organization. 2017. Artemisinin and artemisinin-based combination therapy resistance, WHO
  32. Zardecki, C., Dutta, S., Goodsell, D.S., Voigt, M. & Burley, S.K. 2016. RCSB Protein Data Bank: A Resource for Chemical, Biochemical, and Structural Explorations of Large and Small Biomolecules, J. Chem. Edu., 93(3):569-575. https://doi.org/10.1021/acs.jchemed.5b00404

Last update: 2021-04-19 11:46:48

No citation recorded.

Last update: 2021-04-19 11:46:48

No citation recorded.