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Exploration of bioactive compounds from Mangifera indica (Mango) as probable inhibitors of thymidylate synthase and nuclear factor kappa-B (NF-Κb) in colorectal cancer management

  • Misbaudeen Abdul-Hammed ORCID logo EMAIL logo , Isah Adewale Bello , Monsurat Olajide , Ibrahim Olaide Adedotun , Tolulope Irapada Afolabi , Ayobami Abimbola Ibironke and Barakat Dasola Adebayo
Published/Copyright: March 24, 2023
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Physical Sciences Reviews
From the journal Physical Sciences Reviews Volume 9 Issue 3

Abstract

This research is aimed at investigating the anti-colorectal cancer activities of phytochemicals from Mangifera indica (Mango) via the inhibition of thymidylate synthase (TS) and Nuclear Factor kappa B (NF–κB) using computational chemistry tools. Ligands (141 phytochemicals previously isolated from mangoes) and reference drugs (Raltitrexed and Emetine), the drug inhibitors of TS and NF–κB, respectively) were subjected to screening via ADMET profiling, drug-likeness analysis, oral bioavailability, PASS profile, and molecular interactions. Ligands that passed the previously mentioned screening were docked in duplicate against the target receptors (TS and NF–κB) using PyRx software. The mean values were calculated to obtain suitable docking scores. The analysis showed that TS was strongly inhibited by Friedelan-3beta-Ol with its lower binding energy of −9.0 kcal/mol more than Raltitrexed with a binding energy of −8.7 kcal/mol. NF–κB was also inhibited by Friedelan-3beta-Ol and Friedelin with binding energies of −8.0 and −8.1 kcal/mol, respectively, more than Emetine with a binding energy of −6.4 kcal/mol. These two phytochemicals performed much better than the standard drugs, thus selected as the best hits compounds because of their ADMET profile, drug-likeness properties, bioactivity, oral bioavailability, PASS prediction, binding affinities, and their interactions with the amino acids in the active sites of the receptors. Therefore, further studies are necessary for the validation of these claims toward the development of new effective and safer anti-colorectal cancer drugs.

Keywords: colorectal cancer ; drug discovery ; enzyme inhibition ; Mangifera indica ; nuclear factor kappa-B (NF-κB) ; thymidylate synthase
Corresponding author: Misbaudeen Abdul-Hammed, Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology Faculty of Pure and Applied Science, Along Ogbomoso Ilorin Expressway, Ladoke Akintola University of Technology, Ogbomoso, Oyo, 210214, Nigeria; and Computational Biophysical Chemistry Laboratory, Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, Faculty of Pure and Applied Science, Ogbomoso, Oyo, Nigeria, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Arnold, M, Sierra, MS, Laversanne, M, Soerjomataram, I, Jemal, A, Bray, F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017;66:683–91. https://doi.org/10.1136/gutjnl-2015-310912.Search in Google Scholar PubMed

2. Watson, IR, Takahashi, K, Futreal, PA, Chin, L. Emerging patterns of somatic mutations in cancer. Nat Rev Genet 2013;14:703–18. https://doi.org/10.1038/nrg3539.Search in Google Scholar PubMed PubMed Central

3. Fearon, ER. Molecular genetics of colorectal cancer. Annu Rev Pathol 2011;6:479–507. https://doi.org/10.1146/annurev-pathol-011110-130235.Search in Google Scholar PubMed

4. Fischer, J, Walker, LC, Robinson, BA, Frizelle, FA, Church, JM, Eglinton, TW. Clinical implications of the genetics of sporadic colorectal cancer. ANZ J Surg 2019;89:1224–9. https://doi.org/10.1111/ans.15074.Search in Google Scholar PubMed

5. Guinney, J, Dienstmann, R, Wang, X, de Reynies, A, Schlicker, A, Soneson, C, et al.. The consensus molecular subtypes of colorectal cancer. Nat Med 2015;21:1350–6. https://doi.org/10.1038/nm.3967.Search in Google Scholar PubMed PubMed Central

6. Gao, CM, Ding, JH, Li, SP, Liu, YT, Cao, HX, Wu, JZ, et al.. Polymorphisms in the thymidylate synthase gene and risk of colorectal cancer. Asian Pac J Cancer Prev APJCP 2012;13:4087–91. https://doi.org/10.7314/apjcp.2012.13.8.4087.Search in Google Scholar PubMed

7. Danenberg, PV. Pharmacogenomics of thymidylate synthase in cancer treatment. Front Biosci 2004;9:2484–94. https://doi.org/10.2741/1410.Search in Google Scholar PubMed

8. Yu, LL, Yu, HG, Yu, JP, Luo, HS, Xu, XM, Li, JH. Nuclear factor kappa-B p65 (RelA) transcription factor is constitutively activated in human colorectal carcinoma tissue. World J Gastroenterol 2004;10:3255–60. https://doi.org/10.3748/wjg.v10.i22.3255.Search in Google Scholar PubMed PubMed Central

9. Liu, S, Sun, X, Wang, M, Hou, Y, Zhan, Y, Jiang, Y, et al.. A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NF-kappa B and STAT3 in colorectal cancer cells. Gastroenterology 2014;147:847–59. https://doi.org/10.1053/j.gastro.2014.06.006.Search in Google Scholar PubMed PubMed Central

10. Sakamoto, K, Maeda, S, Hikiba, Y, Nakagawa, H, Hayakawa, Y, Shibata, W, et al.. Constitutive NF-kappa B activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth. Clin Cancer Res 2009;15:2248–58. https://doi.org/10.1158/1078-0432.ccr-08-1383.Search in Google Scholar PubMed

11. Dai, Y, Lawrence, TS, Xu, L. Overcoming cancer therapy resistance by targeting inhibitors of apoptosis proteins and nuclear factor-kappa B. Am. J. Transl. Res. 2009;1:1–15.Search in Google Scholar

12. Seymour, MT, Maughan, TS, Ledermann, JA, Topham, C, James, R, Gwyther, SJ, et al.. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomized controlled trial. Lancet 2007;370:143–52. https://doi.org/10.1016/s0140-6736(07)61087-3.Search in Google Scholar PubMed

13. Onawole, AT, Sulaiman, KO, Adegoke, RO, Kolapo, TU. Identification of potential inhibitors against the Zika virus using consensus scoring. J Mol Graph Model 2017;73:54–61. https://doi.org/10.1016/j.jmgm.2017.01.018.Search in Google Scholar PubMed

14. Sulaiman, KO, Kolapo, TU, Onawole, AT, Islam, A, Adegoke, RO, Badmus, SO. Molecular dynamics and combined docking studies for the identification of zaire ebola virus inhibitors. J Biomol Struct Dyn 2018;37:3029–40. https://doi.org/10.1080/07391102.2018.1506362.Search in Google Scholar PubMed

15. Abdul-Hammed, M, Adedotun, IO, Olajide, M, Irabor, CO, Afolabi, TI, Gbadebo, IO, et al.. Virtual screening, ADMET profiling, PASS prediction, and bioactivity studies of potential inhibitory roles of alkaloids, phytosterols, and flavonoids against COVID-19 main protease (Mpro). Nat Prod Res 2022;36:3110–6.10.1080/14786419.2021.1935933Search in Google Scholar PubMed PubMed Central

16. Abdul-Hammed, M, Adedotun, IO, Falade, VA, Adepoju, AJ, Olasupo, SB, Akinboade, MW. Target-based drug discovery, ADMET profiling and bioactivity studies of antibiotics as potential inhibitors of SARS-CoV-2 main protease (Mpro). VirusDis 2021;32:642–56. https://doi.org/10.1007/s13337-021-00717-z.Search in Google Scholar PubMed PubMed Central

17. Meran, KE, Kamani, T, Sameera, RS. A review on ethnopharmacological applications, pharmacological activities, and bioactive compounds of Mangifera indica (Mango). Evid.-based complement. Alternative Med 2017;2017:6949835. https://doi.org/10.1155/2017/6949835.Search in Google Scholar PubMed PubMed Central

18. Abdusalam, AAA, Murugaiyah, V. Identification of potential inhibitors of 3CL protease of SARS-CoV-2 from ZINC database by molecular docking-based virtual screening. Front Mol Biosci 2020;7:419. https://doi.org/10.3389/fmolb.2020.603037.Search in Google Scholar PubMed PubMed Central

19. Maia, EHB, Assis, LC, de Oliveira, TA, da Silva, AM, Taranto, AG. Structure-based virtual screening: from classical to artificial intelligence. Front Chem 2020;8:343. https://doi.org/10.3389/fchem.2020.00343.Search in Google Scholar PubMed PubMed Central

20. Brogi, S, Ramalho, TC, Kuca, K, Medina-Franco, JL, Valko, M. In silico methods for drug design and discovery. Front Chem 2020;8:612. https://doi.org/10.3389/fchem.2020.00612.Search in Google Scholar PubMed PubMed Central

21. Ferreira, LG, Santos, RN, Oliva, G, Andricopulo, AD. Molecular docking and structure-based drug design strategies. Molecules 2015;20:13384–421. https://doi.org/10.3390/molecules200713384.Search in Google Scholar PubMed PubMed Central

22. Surabhi, SBK. Computer aided drug design: an overview. J Drug Deliv Therapeut 2018;8:504–9. https://doi.org/10.22270/jddt.v8i5.1894.Search in Google Scholar

23. Abdul-Hammed, M, Semire, B, Adepoju, AJ, Adedotun, IO, Lawal, TA, Olajide, M, et al.. Dietary ceramides as inhibitors of cyclooxygenase-2 and thymidylate synthase: insights from DFT and. Molecular Docking Studies 2020;25:Xx.Search in Google Scholar

24. Amin, MR, Yasmin, F, Dey, S, Mahmud, S, Saleh, MA, Emran, TB, et al.. Methyl β-D-galactopyranoside esters as potential inhibitors for SARS-CoV-2 protease enzyme: synthesis, antimicrobial, PASS, molecular docking, molecular dynamics simulations and quantum computations. Glycoconj J 2021. https://doi.org/10.1007/s10719-021-10039-3.Search in Google Scholar PubMed PubMed Central

25. Nisha, CM, Kumar, A, Gupta, PNN, Silakari, C, Tripathi, T, Kumar, A, et al.. Molecular docking and in silico ADMET study reveals acylguanidine 7a as a potential inhibitor of β-secretase. Adv Bioinf 2016;2016:9258578. https://doi.org/10.1155/2016/9258578.Search in Google Scholar PubMed PubMed Central

26. BIOVIA, DS. Discovery Studio Visualizer. San Diego: Dassault Systèmes; 2019.Search in Google Scholar

27. Tian, W, Chen, C, Lei, X, Zhao, J, Liang, J. CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res 2018;46:W363–7. https://doi.org/10.1093/nar/gky473.Search in Google Scholar PubMed PubMed Central

28. Cheng, F, Li, W, Zhou, Y, Shen, J, Wu, Z, Liu, G, et al.. A comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 2012;52:3099–105. https://doi.org/10.1021/ci300367a.Search in Google Scholar PubMed

29. Hongbin, Y, Chaofeng, L, Lixia, S, Jie, L, Yingchun, C, Zhuang, W, et al.. admetSAR 2.0: web service for prediction and optimization of chemical ADMET properties. Bioinformatics 2018;35:1067–9. https://doi.org/10.1093/bioinformatics/bty707.Search in Google Scholar PubMed

30. Lipinski, CA. Lead and drug-like compounds: the rule of five revolutions. Drug Discovery Today: Technologies; 2004:1740–6749 pp.10.1016/j.ddtec.2004.11.007Search in Google Scholar PubMed

31. Lipinski, CA, Lombardo, F, Dominy, BW, Feeney, PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development. Adv Drug Deliv Rev 2021;46:3–25.10.1016/S0169-409X(00)00129-0Search in Google Scholar PubMed

32. Daina, A, Michielin, O, Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:42717. https://doi.org/10.1038/srep42717.Search in Google Scholar PubMed PubMed Central

33. Filimonov, DA, Lagunin, AA, Gloriozova, TA, Rudik, AV, Druzhilovskii, DS, Pogodin, PV, et al.. Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chem Heterocycl Compd 2014;50:444–57. https://doi.org/10.1007/s10593-014-1496-1.Search in Google Scholar

34. Chen, D, Jansson, A, Sim, D, Larsson, A, Nordlund, P. Structural analyses of human thymidylate synthase reveal a site that may control signal switching between active and inactive states. J Biol Chem 2017;292:13449–458. https://doi.org/10.1074/jbc.m117.787267.Search in Google Scholar

35. Cramer, P, Larson, JC, Verdine, LG, Muller, WC. Structure of the human NF-kB p52 homodimer-DNA complex at 2.1 resolution. EMBO J 1997;16:7078–90. https://doi.org/10.1093/emboj/16.23.7078.Search in Google Scholar PubMed PubMed Central

36. Moore, S. Purpose of ADME studies in drug development; 2021. Available from: https://www.azolifesciences.com/article/Purpose-of-ADME-Studies-in-Drug-Development.aspx.Search in Google Scholar

37. Sander, T. OSIRIS Property Explorer. Organic Chemistry Portal; 2001. Available from: https://www.organic-chemistry.org/prog/peo.10.1002/1099-0690(200110)2001:20<3771::AID-EJOC3771>3.0.CO;2-0Search in Google Scholar

38. Jyotshna, Khare, P, Shanker, K. Mangiferin: a review of sources and interventions for biological activities. BioFactors 2016;42:504–14.10.1002/biof.1308Search in Google Scholar

39. Calderón-Montaño, JM, Burgos-Morón, E, Pérez-Guerrero, C, López-Lázaro, M. A review on the dietary flavonoid kaempferol. Mini-Reviews in Med Chem 2011;11:298–344.10.2174/138955711795305335Search in Google Scholar

40. Falade, VA, Adelusi, TI, Adedotun, IO, Abdul-Hammed, M, Lawal, TA, Agboluaje, SA. In-silico investigation of saponins and tannins as potential inhibitors of SARS-CoV-2 main protease (Mpro). Silico Pharmacol 2021;9:9. https://doi.org/10.1007/s40203-020-00071-w.Search in Google Scholar
Received: 2022-10-31
Accepted: 2023-02-08
Published Online: 2023-03-24

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/psr-2022-0282
Keywords for this article
colorectal cancer; drug discovery; enzyme inhibition; Mangifera indica; nuclear factor kappa-B (NF-κB); thymidylate synthase

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Modern analytical approach in biopolymer characterization
  4. Development of nanocellulose fiber reinforced starch biopolymer composites: a review
  5. Recent developments in sago starch thermoplastic bio-composites
  6. Mechanical degradation of sugar palm crystalline nanocellulose reinforced thermoplastic sugar palm starch (TPS)/poly (lactic acid) (PLA) blend bionanocomposites in aqueous environments
  7. Computational design of the novel building blocks for the metal-organic frameworks based on the organic ligand protected Cu4 cluster
  8. Highly functional nanocellulose-reinforced thermoplastic starch-based nanocomposites
  9. Spectral peak areas do not vary according to spectral averaging scheme used in functional MRS experiments at 3 T with interleaved visual stimulation
  10. Triterpenoids of antibacterial extracts from the leaves of Bersama abyssinica Fresen (Francoaceae)
  11. Immediate effects of atrazine application on soil organic carbon and selected macronutrients and amelioration by sawdust biochar pretreatment
  12. Process configuration of combined ozonolysis and anaerobic digestion for wastewater treatment
  13. Concentration levels and risk assessment of organochlorine and organophosphate pesticide residue in selected cereals and legumes sold in Anambra State, south-eastern Nigeria
  14. XRD and cytotoxicity assay of submitted nanomaterial industrial samples in the Philippines
  15. Comparative study of the photocatalytic degradation of tetracycline under visible light irradiation using Bi24O31Br11-anchored carbonaceous and silicates catalyst support
  16. Xanthoangelol, geranilated chalcone compound, isolation from pudau leaves (Artocarpus kemando Miq.) as antibacterial and anticancer
  17. Barley thermoplastic starch nanocomposite films reinforced with nanocellulose
  18. Integration of chemo- and bio-catalysis to intensify bioprocesses
  19. Fabrication of starch-based packaging materials
  20. Potato thermoplastic starch nanocomposite films reinforced with nanocellulose
  21. Review on sago thermoplastic starch composite films reinforced with nanocellulose
  22. Wheat thermoplastic starch composite films reinforced with nanocellulose
  23. Synergistic effect in bimetallic gold catalysts: recent trends and prospects
  24. Simultaneous removal of methylene blue, copper Cu(II), and cadmium Cd(II) from synthetic wastewater using fennel-based adsorbents
  25. The investigation of the physical properties of an electrical porcelain insulator manufactured from locally sourced materials
  26. Concentration evaluation and risk assessment of pesticide residues in selected vegetables sold in major markets of Port Harcourt South-South Nigeria
  27. Detection of iodine in aqueous extract of plants through modified Mohr’s method
  28. Exploration of bioactive compounds from Mangifera indica (Mango) as probable inhibitors of thymidylate synthase and nuclear factor kappa-B (NF-Κb) in colorectal cancer management
  29. A new sphingoid derivative from Acacia hockii De Wild (Fabaceae) with antimicrobial and insecticidal properties
  30. Protection of wood against bio-attack and research of new effective and environmental friendly fungicides
  31. Computational investigation of Arbutus serratifolia Salisb molecules as new potential SARS-CoV-2 inhibitors
  32. Exploring the solvation of water molecules around radioactive elements in nuclear waste water treatment
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