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Journal of molecular modeling
Aug 20, 2022;28 (9): 266.

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

Andy Gálvez-Rodríguez, Anthuan Ferino-Pérez, Zalua Rodríguez-Riera, Idania Rodeiro Guerra, David Řeha, Babak Minofar, Ulises J Jáuregui-Haza
Author Information
  1. Andy Gálvez-Rodríguez: Instituto Superior de Tecnologías Y Ciencias Aplicadas (InSTEC), Universidad de La Habana, La Habana, 10600, Havana, CP, Cuba.
  2. Anthuan Ferino-Pérez: Department of Chemistry, KU Leuven Chem&Tech, Celestijnenlaan 200F, Bus 2404, 3001, Louvain, Belgium.
  3. Zalua Rodríguez-Riera: Instituto Superior de Tecnologías Y Ciencias Aplicadas (InSTEC), Universidad de La Habana, La Habana, 10600, Havana, CP, Cuba.
  4. Idania Rodeiro Guerra: Departamento de Farmacología, Instituto de Ciencias del Mar, La Habana, 10600, Havana, CP, Cuba.
  5. David Řeha: Laboratory of Structural Biology and Bioinformatics, Institute of Microbiology of the Czech Academy of Sciences, Zamek 136, 37333, Nove Hrady, Czech Republic.
  6. Babak Minofar: Laboratory of Structural Biology and Bioinformatics, Institute of Microbiology of the Czech Academy of Sciences, Zamek 136, 37333, Nove Hrady, Czech Republic.
  7. Ulises J Jáuregui-Haza: Instituto Tecnológico de Santo Domingo (INTEC), Avenida de los Próceres #49, Los Jardines del Norte 10602, Santo Domingo, Dominican Republic. Ulises.jauregui@intec.edu.do.
PMID: 35987945 DOI: 10.1007/s00894-022-05260-2

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. 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.

Keywords

Anti-cancer activity Mangiferin Molecular docking Natural bond analysis QM/MM

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Grants

  1. PN223LH010-029/Ministerio de Ciencia, Tecnología y Medio Ambiente

MeSH Term

Matrix Metalloproteinase 9
NF-kappa B
Tumor Necrosis Factor-alpha
Xanthones

Chemicals

NF-kappa B
Tumor Necrosis Factor-alpha
Xanthones
mangiferin
Matrix Metalloproteinase 9
Journal Article
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0mangiferinMMP-9Mangiferinpropertiesinteractionscomputationalresultsstudyanti-cancerselectivelyworkcharacterizedshowinhibitionZnQM/MMinteractionmolecularmechanismsactivityglycosylatedxanthonewidelydistributednatureexhibitswidepharmacologicalactivitieshighlightinginterferesinflammationlipidcalciumsignalinginhibitsmultipleNFkBtargetgenesinterleukin-6tumornecrosisfactorplasminogenmatrixmetalloproteinaseamongotherspolyphenolNF-κβusingchemistrymethodsmangiferinainteractcatalyticatompenta-coordinatestructurealsodemonstratedstrongchargetransferestablishedConcerningmangiferin/NF-κβsystem923%p50sub-unityDNAmaintainedbindingenergyof - 804 kcal/molfindingsindicateblocksp50-p65/DNAresultinglossfunctionshetero-dimericmembersuggestingcancerprogressionExperimentalconcerningnaturalcompoundcaninhibitNF-ƙβAlthoughanti-tumorwelldefinedactionsdescribedcarriedcharacterizetargetsobtainedcorroborateanti-proliferativeanti-apoptoticprovidedepictionactionExplainingNF-ƙβ:Anti-cancerMoleculardockingNaturalbondanalysis

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