In silico study of polyphenols as potential inhibitors of MALT1 protein in non-Hodgkin lymphoma.
Abas SezerLejla MahmutovićBetul AkcesmePublished in: Medical oncology (Northwood, London, England) (2023)
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.
Keyphrases
- signaling pathway
- molecular docking
- pi k akt
- induced apoptosis
- diffuse large b cell lymphoma
- immune response
- epithelial mesenchymal transition
- molecular dynamics simulations
- cell cycle arrest
- cell proliferation
- epstein barr virus
- amino acid
- dendritic cells
- transcription factor
- small molecule
- cell death
- protein protein
- dna binding