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Explaining the interaction of mangiferin with MMP-9 and NF-ƙβ: a computational study

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Abstract

Mangiferin is a glycosylated xanthone widely distributed in nature, which exhibits wide pharmacological activities, highlighting its anti-cancer properties. Mangiferin interferes with inflammation, lipid, and calcium signaling, which selectively inhibits multiple NFkB target genes as interleukin-6, tumor necrosis factor, plasminogen, and matrix metalloproteinase, among others. In this work, the interactions of this polyphenol with MMP-9 and NF-κβ are characterized by using computational chemistry methods. The results show MMP-9 inhibition by mangiferina is characterized for the interact with the catalytic Zn atom through a penta-coordinate structure. It is also demonstrated through a strong charge transfer established between mangiferin and Zn in the QM/MM study. Concerning the mangiferin/NF-κβ system, the 92.3% of interactions between p50 sub-unity and DNA are maintained with a binding energy of − 8.04 kcal/mol. These findings indicate that mangiferin blocks the p50-p65/DNA interaction resulting in the loss of the functions of this hetero-dimeric member and suggesting inhibition of the cancer progression.

Graphical abstract

Experimental results concerning the anti-cancer properties of mangiferin show that this natural compound can inhibit selectively MMP-9 and NF-ƙβ. Although the anti-tumor properties of mangiferin are well defined, its molecular mechanisms of actions are not described. In this work, a computational study is carried out to characterize the interactions of mangiferin with these molecular targets. The results obtained corroborate the anti-proliferative and anti-apoptotic activity of mangiferin and provide a depiction of its mechanisms of action.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

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References

  1. B. Faubert, A. Solmonson, R. J. DeBerardinis, Science, 2020, 368, eaaw5473.

  2. Malik V, Garg S, Afzal S, Dhanjal JK, Yun CO, Kaul SC, Sundar D, Wadhwa R (2020) Int J Mol Sci 21:5463

    Article  CAS  PubMed Central  Google Scholar 

  3. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F (2021) Int J Cancer 149:778

    Article  CAS  Google Scholar 

  4. Dufour A, Sampson NS, Li J, Kuscu C, Rizzo RC, DeLeon JL, Zhi J, Jaber N, Liu E, Zucker S (2011) Cancer Res 71:4977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mondal S, Adhikari N, Banerjee S, Amin SA, Jha T (2020) Eur J Med Chem 194:112260

    Article  CAS  PubMed  Google Scholar 

  6. Özdemir A, Sever B, Altıntop MD, Temel HE, Atlı O, Baysal M, Demirci F (2017) Molecules 22:1109

    Article  PubMed Central  CAS  Google Scholar 

  7. Sanapalli BKR, Yele V, Jupudi S, Karri VVSR (2021) RSC Adv 11:26820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Aggarwal BB, Sung B (2011) Cancer Discov 1:469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Xu L, Russu WA (2013) Bioorg Med Chem 21:540

    Article  CAS  PubMed  Google Scholar 

  10. Baldwing AS (1996) Annu Rev Immunol 14:649

    Article  Google Scholar 

  11. Ichiki H, Miura T, Kubo M, Ishihara E, Komatsu Y, Tanikawa K, Okada M (1998) Biol Pharm Bull 21:1389

    Article  CAS  PubMed  Google Scholar 

  12. Lin H, Chen R, Liu X, Sheng F, Zhang H (2010) Spectrochim Acta, Part A 75:1584

    Article  CAS  Google Scholar 

  13. Dar A, Faizi S, Naqvi S, Roome T, Zikr-ur-Rehman S, Ali M, Firdous S, Moin ST (2005) Biol Pharm Bull 28:596

    Article  CAS  PubMed  Google Scholar 

  14. Hernandez P, Rodriguez PC, Delgado R, Walczak H (2007) Pharmacol Res 55:167

    Article  CAS  PubMed  Google Scholar 

  15. Beltrán AE, Alvarez Y, Xavier FE, Hernanz R, Rodriguez J, Núñez AJ, Alonso MJ, Salaices M (2004) Eur J Pharmacol 499:297

    Article  PubMed  CAS  Google Scholar 

  16. Garrido G, González D, Lemus Y, Garcıa D, Lodeiro L, Quintero G, Delporte C, Núñez-Sellés AJ, Delgado R (2004) Pharmacol Res 50:143

    Article  PubMed  Google Scholar 

  17. Guha S, Ghosal S, Chattopadhyay U (1996) Chemotherapy 42:443

    Article  CAS  PubMed  Google Scholar 

  18. A. J. Núñez Selles, M. Daglia, L. Rastrelli, BioFactors, 2016, 42, 475.

  19. Khurana RK, Kaur R, Lohan S, Singh KK, Singh B (2016) Pharm Pat Anal 5:169

    Article  CAS  PubMed  Google Scholar 

  20. Li H, Huang J, Yang B, Xiang T, Yin X, Peng W, Cheng W, Wan J, Luo F, Li H (2013) Toxicol Appl Pharmacol 272:180

    Article  CAS  PubMed  Google Scholar 

  21. Takeda T, Tsubaki M, Kino T, Yamagishi M, Lida M, Itoh T, Imano M, Tanabe G, Muraoka O, Satou T (2016) Chem-Biol Interact 251:26

    Article  CAS  PubMed  Google Scholar 

  22. Jinson G, Li L, Zian Z, Cheng X, Junjian Z (2015) Oncol Rep 33:2815

    Article  CAS  Google Scholar 

  23. Ji-Sun J, Kangsik J, Dong-Hyun K, Hee-Sun K (2010) Pharmacol Res 66:95

    Google Scholar 

  24. M. Imran, M. Sajid Arshad, M. Sadiq Butt, J. H. Kwon, M. Umair Arshad, M. Tauseef Sultan, Lipids Health Dis. 2017, 16, 1.

  25. Garrido G, Blanco-Molina M, Sancho R, Macho A, Delgado R, Muñoz M (2005) Phytother Res 19:211

    Article  CAS  PubMed  Google Scholar 

  26. HyperChem Professional Release v7.01 for Windows. 2002, Hypercube Inc.: Gainesville, FL.

  27. Stewart JJ (2013) J Mol Model 19:1

    Article  CAS  PubMed  Google Scholar 

  28. W. Thiel, Theor. App. Comput. Chem. 2005, 559.

  29. Parr RG, Yang W (1996) J Phys Chem 100:12974

    Article  Google Scholar 

  30. DiLabio GA, Johnson ER, Otero-de-la-Roza A (2013) Phys Chem Chem Phys 15:12821

    Article  CAS  PubMed  Google Scholar 

  31. Ebadi A, Noei M (2017) J Mol Model 23:38

    Article  PubMed  CAS  Google Scholar 

  32. Peverati R (2014) D G Truhlar 372:20120476

    Google Scholar 

  33. Grimme S, Antony J, Ehrlich S, Krieg H (2010) J Chem Phys 132:154104

    Article  PubMed  CAS  Google Scholar 

  34. Marenich AV, Cramer CJ, Truhlar DG (2009) J Phys Chem 113:6378

    Article  CAS  Google Scholar 

  35. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, J. E. Peralta, F. Gliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski,D. J Fox, Gaussian 09, Revision E.01. 2013, Gaussian, Inc.: Wallingford CT.

  36. Stewart JJP, MOPAC2016 (2016) Stewart Computational Chemistry: Colorado Springs, CO, USA

  37. Oreluk J, Liu Z, Hegde A, Li W, Packard A, Frenklach M, Zubarev D (2018) Sci Rep 8:13248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Reed AE, Curtiss LA, Weinhold F (1988) Chem Rev 88:899

    Article  CAS  Google Scholar 

  39. Bhattacharjee R, Majumder T, Datta A (2019) J Comput Chem 40:1488

    Article  CAS  PubMed  Google Scholar 

  40. Sebastian S, Sundaraganesan N (2010) Spectrochim Acta, Part A 75:941

    Article  CAS  Google Scholar 

  41. Subashchandrabose S, Krishnan AR, Saleem H, Parameswari R, Sundaraganesan N, Thanikachalam V, Manikandan G (2010) Spectrochim Acta, Part A 77:877

    Article  CAS  Google Scholar 

  42. E. D. Glendenning, A. E. Reed, J. E. Carpenter, F. Weinhold, 2001, Gaussian Inc.: Pittsburg, PA, US.

  43. Lu T, Chen F (2012) J Comput Chem 33:580

    PubMed  Google Scholar 

  44. R. D. Dennington, T. A. Keith, J. M. Millam, 2008, GaussView 5.0. Gaussian, Inc.

  45. Durrant JD, McCammon JA (2011) J Mol Graphics Modell 29:888

    Article  CAS  Google Scholar 

  46. Hu X, Balaz S, Shelver WHJ (2004) J Mol Graphics Modell 22:293

    Article  CAS  Google Scholar 

  47. Hu X, Shelver WHJ (2003) J Mol Graphics Modell 22:115

    Article  CAS  Google Scholar 

  48. Hou X, Du J, Zhang J, Du L, Fang H, Li M (2013) J Chem Inf Model 53:188

    Article  CAS  PubMed  Google Scholar 

  49. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) J Comput Chem 30:2785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Rowsell S, Maciel FV, Hawtin P, Minshull CA, Jepson H, Brockbank SMV, Barratt DG, Slater AM, McPheat WL, Waterson D, Henney AM, Pauptit RA (2002) J Mol Biol 319:173

    Article  CAS  PubMed  Google Scholar 

  51. Chen FE, Huang DB, Chen YQ, Ghosh G (1998) Nature 391:410

    Article  CAS  PubMed  Google Scholar 

  52. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) J Cheminf 3:1

    Article  CAS  Google Scholar 

  53. G. Klebe, H. Li, J. H. Jensen, J. E. Nielsen, P. Czodrowski, T. J. Dolinsky, N. A. Baker, Nucleic Acids Res. 2007, 35(suppl_2), W522.

  54. J. A. McCammon, J. E. Nielsen, N. A. Baker, T. J. Dolinsky, Nucleic Acids Res. 2004, 32(suppl_2), W665.

  55. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) J Comput Chem 25:1157

    Article  CAS  PubMed  Google Scholar 

  56. Gasteiger J, Marsili M (1980) Tetrehaedron 36:3219

    Article  CAS  Google Scholar 

  57. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) J Comput Chem 19:1639

    Article  CAS  Google Scholar 

  58. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) J Comput Chem 25:1157

    Article  CAS  PubMed  Google Scholar 

  59. Bayly CI, Cieplak P, Cornell W, Kollman PA (1993) J Phys Chem 97:10269

    Article  CAS  Google Scholar 

  60. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) J Comput Chem 19:1639

    Article  CAS  Google Scholar 

  61. Berendsen HJ, van der Spoel D, van Drunen R (1995) Comput Phys Commun 91:43

    Article  CAS  Google Scholar 

  62. Lindahl E, Hess B, van Der Spoel D (2001) J Mol Mod 7:306

    Article  CAS  Google Scholar 

  63. van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ (2005) J Comput Chem 26:1701

    Article  CAS  Google Scholar 

  64. Zhao Y, Truhlar DG (2008) Theor Chem Acc 120:215

    Article  CAS  Google Scholar 

  65. Boys SF, Bernardi F (1970) Mol Phys 19:553

    Article  CAS  Google Scholar 

  66. Simon S, Duran M, Dannenberg JJ (1996) J Chem Phys 105:11024

    Article  CAS  Google Scholar 

  67. Mardirossian N, Head-Gordon M (2017) Mol Phys 115:2315

    Article  CAS  Google Scholar 

  68. Nowroozi A, Raissi H, Hajiabadi H, Mm Jahani P (2011) Int J Quantum Chem 111:3040

    Article  CAS  Google Scholar 

  69. Shainyan BA, Chipanina NN, Aksamentova TN, Oznobikhina LP, Rosentsveig GN, Rosentsveig IB (2010) Tetrahedron 66:8551

    Article  CAS  Google Scholar 

  70. Sosa GL, Peruchena NM, Contreras RH, Castro EA (2002) J Mol Struct: THEOCHEM 577:209

    Article  Google Scholar 

  71. da Veiga AA, Bragança VAN, Holanda LHC, Braga RP Jr, Sousa AC, Santos KL, Vale JK, Borges RS (2021) Chem Data Collect 31:10062

    Article  CAS  Google Scholar 

  72. Alberts IL, Nadassy K, Wodak SJ (1998) Protein Sci 7:1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Rouffet M, Denhez C, Bourguet E, Bohr F, Guillaume D (2009) Org Biomol Chem 7:3817

    Article  CAS  PubMed  Google Scholar 

  74. Browner MF, Smith WW, Castelhano AL (1995) Biochemistry 34:6602

    Article  CAS  PubMed  Google Scholar 

  75. Pavlovsky AG, Williams MG, Ye Q-Z, Ortwine DF, Purchase CF, White AD, Dhanaraj V, Roth BD, Johnson LL, Hupe D (1999) Protein Sci 8:1455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Yamamoto D, Takai S, Jin D, Inagaki S, Tanaka K, Miyazaki M (2007) J Mol Cell Cardiol 43:670

    Article  CAS  PubMed  Google Scholar 

  77. Tochowicz A, Maskos K, Huber R, Oltenfreiter R, Dive V, Yiotakis A, Zanda M, Bode W, Goettig P (2007) J Mol Biol 371:989

    Article  CAS  PubMed  Google Scholar 

  78. Tsai K-C, Teng L-W, Shao Y-M, Chen Y-C, Lee Y-C, Li M, Hsiao N-W (2009) Bioorg Med Chem Lett 19:5665

    Article  CAS  PubMed  Google Scholar 

  79. Shoji K, Tsubaki M, Yamazoe Y, Satou T, Itoh T, Kidera Y, Tanimori Y, Yanae M, Matsuda H, Taga A (2011) Arch Pharmacal Res 34:469

    Article  CAS  Google Scholar 

  80. Murphy RB, Philipp DM, Friesner RA (2000) J Comput Chem 21:1442

    Article  CAS  Google Scholar 

  81. Philipp DM, Friesner RA (1999) J Comput Chem 20:1468

    Article  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank the Informatic Service of InSTEC at Havana, Cuba; Raphael Pasquier, Jacques Laminie, and Pascal Poullet for their support with the calculation facilities that have been performed using Wahoo; and the cluster of the Centre Commun de Calcul Intensif of the “Université des Antilles”, Guadeloupe, France. This work received funds from the Office of Management of Funds and International Projects of the Ministry of Science, Technology and Environment of the Republic of Cuba, project PN223LH010-029.

Funding

Ministerio de Ciencia, Tecnología y Medio Ambiente (PN223LH010-029) funded this study.

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Authors and Affiliations

  1. Instituto Superior de Tecnologías Y Ciencias Aplicadas (InSTEC), Universidad de La Habana, La Habana, 10600, Havana, CP, Cuba

    Andy Gálvez-Rodríguez & Zalua Rodríguez-Riera

  2. Department of Chemistry, KU Leuven Chem&Tech, Celestijnenlaan 200F, Bus 2404, 3001, Louvain, Belgium

    Anthuan Ferino-Pérez

  3. Departamento de Farmacología, Instituto de Ciencias del Mar, La Habana, 10600, Havana, CP, Cuba

    Idania Rodeiro Guerra

  4. Laboratory of Structural Biology and Bioinformatics, Institute of Microbiology of the Czech Academy of Sciences, Zamek 136, 37333, Nove Hrady, Czech Republic

    David Řeha & Babak Minofar

  5. Instituto Tecnológico de Santo Domingo (INTEC), Avenida de los Próceres #49, Los Jardines del Norte 10602, Santo Domingo, Dominican Republic

    Ulises J. Jáuregui-Haza

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  1. Andy Gálvez-Rodríguez
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Contributions

Conceptualization, methodology, writing — original draft, data curation, validation, supervision, writing — review and editing: UJJH; methodology, writing — original draft, calculations, data curation, writing — review and editing: AGR and AFP; writing — original draft, calculations, data curation, writing — review and editing: DR and BM; validation, supervision, writing — review and editing: ZRR and IRG.

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Correspondence to Ulises J. Jáuregui-Haza.

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Gálvez-Rodríguez, A., Ferino-Pérez, A., Rodríguez-Riera, Z. et al. Explaining the interaction of mangiferin with MMP-9 and NF-ƙβ: a computational study. J Mol Model 28, 266 (2022). https://doi.org/10.1007/s00894-022-05260-2

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