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.

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

Department of Chemistry KU Leuven Chem and Tech Celestijnenlaan 200F Bus 2404 3001 Louvain Belgium

Instituto Superior de Tecnologías Y Ciencias Aplicadas Universidad de La Habana La Habana 10600 Havana CP Cuba

Instituto Tecnológico de Santo Domingo Avenida de los Próceres 49 Los Jardines del Norte 10602 Santo Domingo Dominican Republic

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

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