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In silico study of polyphenols as potential inhibitors of MALT1 protein in non-Hodgkin lymphoma

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Abstract

Non-Hodgkin lymphoma (NHL) is one of the most common cancer types. Deregulated signaling pathways can trigger certain NHL subtypes, including Diffuse Large B-cell lymphoma. NF-ĸB signaling pathway, which is responsible for the proliferation, growth, and survival of cells, has an essential role in lymphoma development. Although different signals control NF-ĸB activation in various lymphoid malignancies, the characteristic one is the CARD11-BCL10-MALT1 (CBM) complex. The CBM complex is responsible for the initiation of adaptive immune response. Our study is focused on the molecular docking of ten polyphenols as potential CARD11-BCL10-MALT1 complex inhibitors, essentially through MALT1 inhibition. Molecular docking was performed by Auto Dock Tools and AutoDock Vina tool, while SwissADME was used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of the ligands. Out of 66 ligands that were used in this study, we selected and visualized five. Selection criteria were based on the binding energy score and position of the ligands on the used protein. 2D and 3D visualizations showed interactions of ligands with the protein. Five ligands are considered potential inhibitors of MALT1, thus affecting NF-ĸB signaling pathway. However, additional in vivo and in vitro studies are required to confirm their mechanism of inhibition.

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Data availability

Data analyzed in this study have been either provided or are publicly available in the referred databases.

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Authors and Affiliations

  1. Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička Cesta 15, 71000, Sarajevo, Bosnia and Herzegovina

    Abas Sezer, Lejla Mahmutović & Betül Akçeşme

  2. Department of Basic Medical Sciences, Division of Medical Biology, University of Health Sciences, 34000, Istanbul, Turkey

    Betül Akçeşme

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  1. Abas Sezer
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  2. Lejla Mahmutović
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Abas Sezer. Writing, review, and editing were performed by LM, while conceptualization and supervision were performed by BA. The first draft of the manuscript was written by AS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Betül Akçeşme.

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Sezer, A., Mahmutović, L. & Akçeşme, B. In silico study of polyphenols as potential inhibitors of MALT1 protein in non-Hodgkin lymphoma. Med Oncol 41, 37 (2024). https://doi.org/10.1007/s12032-023-02261-w

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