In silico Screening of Potential Antidiabetic Phenolic Compounds from Banana (Musa spp.) Peel Against PTP1B Protein

https://doi.org/10.22146/jtbb.83124

Rico Alexander Pratama(1), Junaida Astina(2), Arli Aditya Parikesit(3*)

(1) Department of Food Science and Nutrition, School of Life Sciences, Indonesia International Institute for Life Sciences (i3L), Jalan Pulomas Barat Kav 88, East Jakarta 13210, Indonesia
(2) Department of Food Science and Nutrition, School of Life Sciences, Indonesia International Institute for Life Sciences (i3L), Jalan Pulomas Barat Kav 88, East Jakarta 13210, Indonesia
(3) Department of Bioinformatics, School of Life Sciences, Indonesia International Institute for Life Sciences (i3L), Jalan Pulomas Barat Kav 88, East Jakarta 13210, Indonesia
(*) Corresponding Author

Abstract


Type 2 diabetes mellitus (T2DM) is a global problem with increasing prevalence. The current treatments have made an immense progress  with some side effects, such as drug resistance, acute kidney toxicity, and increased risk of heart attack. Banana (Musa spp.) peel comprises 40% of banana fruit contains high phenolic compounds whilst some studies have suggested a correlation between phenolic compounds and antidiabetic activity. One of the novel protein targets that has been identified as a potential anti-diabetic treatment is PTP1B (PDB ID:2NT7). Therefore, this study aimed to screen the potential PTP1B inhibitor for antidiabetic treatment from phenolic compounds in banana peel. QSAR, molecular docking, ADME-Tox, and molecular dynamics analysis were deployed to examine forty-three phenolic compounds in banana peel. Eighteen ligands were screened by QSAR analysis and eight of them had a lower binding energy than the standard (ertiprotafib) in molecular docking, with urolithin A and chrysin were the lowest. Both passed Lipinski’s rule of five, had a good intestinal absorption, and no blood-brain barrier penetration, however, their mutagenicity, carcinogenicity, and irritation to the skin and eyes were still in questions. Molecular dynamics analysis found both of them were in a stable conformation with PTP1B. This study suggested a potential of urolithin A and chrysin as PTP1B inhibitor for antidiabetic treatment. Additionally, further experimentation is required to validate this finding.

 

 


Keywords


antidiabetic; banana peel; diabetes mellitus; in silico; phenolic compound; PTP1B

Full Text:

PDF


References

Aboul-Enein, A.M. et al., 2016. Identification of phenolic compounds from banana peel (Musa paradaisica L.) as antioxidant and antimicrobial agents. Journal of Chemical and Pharmaceutical Research, 8(4), pp.46–55.

Acevedo, S.A. et al., 2021. Recovery of Banana Waste-Loss from Production and Processing: A Contribution to a Circular Economy. Molecules (Basel, Switzerland), 26(17), 5282. doi: 10.3390/molecules26175282.

Aryaeian, N., Sedehi, S.K. & Arablou, T., 2017. Polyphenols and their effects on diabetes management: A review. Medical journal of the Islamic Republic of Iran, 31(1), pp.886–892. doi: 10.14196/MJIRI.31.134.

Asgar, A., 2013. Anti-diabetic potential of phenolic compounds: A review. International Journal of Food Properties, 16(1), pp.91–103. doi: 10.1080/10942912.2011.595864.

Aurora, Y. et al., 2022. Identification of Flavonoids of Kalanchoe Pinnata as Candidate Drugs for COVID-19 Gamma-Variant Treatment. Malaysian Journal of Fundamental and Applied Sciences, 18(6), pp.630-643. doi: 10.11113/MJFAS.V18N6.2594

Bashmil, Y.M. et al., 2021. Screening and Characterization of Phenolic Compounds from Australian Grown Bananas and Their Antioxidant Capacity. Antioxidants, 10(10), 1521. doi: 10.3390/ANTIOX10101521.

Bickerton, G.R. et al., 2012. Quantifying the chemical beauty of drugs. Nature Chemistry, 4(2), pp.90–98. doi: 10.1038/nchem.1243.

BIOVIA Systèmes Dassault, 2019. BIOVIA Discovery Studio.

Burley, S.K. et al., 2021. RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. Nucleic Acids Research, 49(D1), pp.D437–D451. doi: 10.1093/NAR/GKAA1038.

Chatterjee, S., Khunti, K. & Davies, M.J., 2017. Type 2 diabetes. The Lancet, 389(10085), pp.2239–2251. doi: 10.1016/S0140-6736(17)30058-2.

Chen et al., 2009. Investigation of atomic level patterns in protein—small ligand interactions. PLoS ONE, 4(2), e4473. doi: 10.1371/journal.pone.0004473

Dahlén, A.D. et al., 2022. Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales. Frontiers in Pharmacology, 12, 4119. doi: 10.3389/FPHAR.2021.807548/BIBTEX.

Dallakyan, S. & Olson, A.J., 2015. Small-molecule library screening by docking with PyRx. Methods in Molecular Biology, 1263, pp.243–250. doi: 10.1007/978-1-4939-2269-7_19/COVER.

Damián-Medina, K. et al., 2020. In silico analysis of antidiabetic potential of phenolic compounds from blue corn (Zea mays L.) and black bean (Phaseolus vulgaris L.). Heliyon, 6(3), e03632. doi: 10.1016/J.HELIYON.2020.E03632.

Dhorajiwala, T.M., Halder, S.T. & Samant, L., 2019. Comparative In Silico Molecular Docking Analysis of L-Threonine-3-Dehydrogenase, a Protein Target Against African Trypanosomiasis Using Selected Phytochemicals. Journal of Applied Biotechnology Reports, 6(3), pp.101–108. doi: 10.29252/JABR.06.03.04.

Eberhardt, J. et al., 2021. AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of Chemical Information and Modeling, 61(8), pp.3891–3898. doi: 10.1021/ACS.JCIM.1C00203/SUPPL_FILE/CI1C00203_SI_002.ZIP.

Eleftheriou, P., Geronikaki, A. & Petrou, A., 2019. PTP1b Inhibition, A Promising Approach for the Treatment of Diabetes Type II. Current topics in medicinal chemistry, 19(4), pp.246–263. doi: 10.2174/1568026619666190201152153.

Filimonov, D.A. et al., 2014. Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chemistry of Heterocyclic Compounds, 50(3), pp.444–457. doi: 10.1007/S10593-014-1496-1/METRICS.

Föllmann, W. et al., 2013. Ames Test. In Brenner’s Encyclopedia of Genetics: Second Edition. Academic Press, pp.104–107. doi: 10.1016/B978-0-12-374984-0.00048-6.

Food and Agriculture Organization of the United Nations, 2022, 'FAOSTAT' in Food and Agriculture Organization of the United Nations, viewed 16 February 2023, from https://www.fao.org/

Galicia-Garcia, U. et al., 2020. Pathophysiology of Type 2 Diabetes Mellitus. International Journal of Molecular Sciences, 21(17), pp.1–34. doi: 10.3390/IJMS21176275.

Goyal, R. & Jialal, I., 2020, 'Diabetes Mellitus Type 2' in StatPearls, viewed 5 February 2023, from https://www.ncbi.nlm.nih.gov/books/NBK513253/?report=classic

Gutiérrez-Grijalva, E.P. et al., 2016. Review: dietary phenolic compounds, health benefits and bioaccessibility. Archivos Latinoamericaos de Nutrición, 66(2).

Haj, F.G. et al., 2005. Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B-/- mice. Journal of Biological Chemistry, 280(15), pp.15038–15046. doi: 10.1074/jbc.M413240200.

Hussain, S.M. et al., 2016. Characterization of isolated bioactive phytoconstituents from Flacourtia indica as potential phytopharmaceuticals-An in silico perspective. Journal of Pharmacognosy and Phytochemistry, 5(6), pp.323-331.

Kanwal, A. et al., 2022. Exploring New Drug Targets for Type 2 Diabetes: Success, Challenges and Opportunities. Biomedicines, 10(2), 331. doi: 10.3390/BIOMEDICINES10020331.

Kim, D.H. et al., 2016. Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential. BioMed research international, 2016, 8432759. doi: 10.1155/2016/8432759.

Kim, S. et al., 2021. PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Research, 49(D1), pp.D1388–D1395. doi: 10.1093/NAR/GKAA971.

Kukic, P. & Nielsen, J.E., 2010. Electrostatics in proteins and protein–ligand complexes. Future Medicinal Chemistry, 2(4), pp.647-66. doi: 10.4155/fmc.10.6

Kuriata, A. et al., 2018. CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures. Nucleic Acids Research, 46(W1), pp.W338–W343. doi: 10.1093/NAR/GKY356.

Kusuma, S.M.W., Utomo, D.H. & Susanti, R., 2022. Molecular Mechanism of Inhibition of Cell Proliferation: An In Silico Study of the Active Compounds in Curcuma longa as an Anticancer. Journal of Tropical Biodiversity and Biotechnology, 7(3), 74905. doi: https://doi.org/10.22146/jtbb.74905

Liu, R. et al., 2022. Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives. International Journal of Molecular Sciences, 23(13), 7027. doi: 10.3390/IJMS23137027.

Lopina, O.D., 2017. Enzyme Inhibitors and Activators. InTech. doi: 10.5772/67248.

Mechchate, H. et al., 2021. Insight into Gentisic Acid Antidiabetic Potential Using In Vitro and In Silico Approaches. Molecules, 26(7), 1932. doi: 10.3390/MOLECULES26071932.

Mudunuri, G.R. et al., 2022. Novel In Silico and In Vivo Insights of Flavonoids as Anti-Diabetic and Anti-Oxidant in Rodent Models. Indian Journal of Pharmaceutical Sciences, 84(4), pp.1041–1050. doi: 10.36468/PHARMACEUTICAL-SCIENCES.998.

Naz, D. et al., 2019. In vitro and in vivo Antidiabetic Properties of Phenolic Antioxidants From Sedum adenotrichum. Frontiers in Nutrition, 6, 177. doi: 10.3389/fnut.2019.00177

Parikesit, A.A. & Nurdiansyah, R., 2021. Virtual screening of lead compounds for SARS-CoV-2. J Pharm Pharmacogn Res, 9(5), pp.730-745.

Praparatana, R. et al., 2022. Flavonoids and Phenols, the Potential Anti-Diabetic Compounds from Bauhinia strychnifolia Craib. Stem. Molecules, 27(8), 2393. doi: 10.3390/MOLECULES27082393.

Pratama, M.R.F. et al., 2022. Introducing a Two‐Dimensional Graph of Docking Score Difference vs. Similarity of Ligand‐Receptor Interactions. Indonesian Journal of Biotechnology, 26(1), pp.54-60. doi: 10.22146/ijbiotech.62194

Rath, P. et al., 2022. Potential Therapeutic Target Protein Tyrosine Phosphatase-1B for Modulation of Insulin Resistance with Polyphenols and Its Quantitative Structure–Activity Relationship. Molecules, 27(7), 2212. doi: 10.3390/MOLECULES27072212.

Salehi, B. et al., 2019. Antidiabetic Potential of Medicinal Plants and Their Active Components. Biomolecules, 9(10), 551. doi: 10.3390/BIOM9100551.

Sharma, R., Oberoi, H.S. & Dhillon, G.S., 2016. Fruit and Vegetable Processing Waste: Renewable Feed Stocks for Enzyme Production. Agro-Industrial Wastes as Feedstock for Enzyme Production: Apply and Exploit the Emerging and Valuable Use Options of Waste Biomass, pp.23–59. doi: 10.1016/B978-0-12-802392-1.00002-2.

Suleria, H.A.R., Barrow, C.J. & Dunshea, F.R., 2020. Screening and Characterization of Phenolic Compounds and Their Antioxidant Capacity in Different Fruit Peels. Foods 9(9), 1206. doi: 10.3390/FOODS9091206.

Tautz, L., Critton, D.A. & Grotegut, S., 2013. Protein tyrosine phosphatases: Structure, function, and implication in human disease. Methods in Molecular Biology, 1053, pp.179–221. doi: 10.1007/978-1-62703-562-0_13/COVER.

Wicaksono, A. et al., 2022. Screening Rafflesia and Sapria Metabolites Using a Bioinformatics Approach to Assess Their Potential as Drugs. Philippine Journal of Science, 151(5), pp.1771–1791. doi: 10.56899/151.05.20.

Wijaya, R.M. et al., 2021. Covid-19 in silico drug with zingiber officinale natural product compound library targeting the mpro protein. Makara Journal of Science, 25(3), pp.162–171. doi: 10.7454/mss.v25i3.1244.

Wisnumurti, R.F., Aslanzadeh, S. & Aditya Parikesit, A., 2022. Computational examination of flavonoid compounds: Utilization of molecularsimulation to discover drug candidates for Covid-19. Rasayan J. Chem, 15(2), pp.1132-1136. doi: 10.31788/RJC.2022.1526877.

Wojdyło, A. et al., 2016. Phenolic compounds, antioxidant and antidiabetic activity of different cultivars of Ficus carica L. fruits. Journal of Functional Foods, 25, pp.421–432. doi: 10.1016/J.JFF.2016.06.015.

Xiong, G. et al., 2021. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Research, 49(W1), pp.W5–W14. doi: 10.1093/NAR/GKAB255.

Zhang, Y. & Du, Y., 2018. The development of protein tyrosine phosphatase1B inhibitors defined by binding sites in crystalline complexes. Future Med. Chem., 10(19), pp.2345–2367. doi: 10.4155/FMC-2018-0089.



DOI: https://doi.org/10.22146/jtbb.83124

Article Metrics

Abstract views : 2156 | views : 840

Refbacks

  • There are currently no refbacks.


Copyright (c) 2023 Journal of Tropical Biodiversity and Biotechnology

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Editoral address:

Faculty of Biology, UGM

Jl. Teknika Selatan, Sekip Utara, Yogyakarta, 55281, Indonesia

ISSN: 2540-9581 (online)