New Insights for Polyphenolic Compounds as Naturally Inspired Proteasome Inhibitors
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Published:2023-12-11
Issue:12
Volume:16
Page:1712
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ISSN:1424-8247
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Container-title:Pharmaceuticals
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language:en
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Short-container-title:Pharmaceuticals
Author:
Marchese Emanuela1ORCID, Gallo Cantafio Maria Eugenia2, Ambrosio Francesca Alessandra2ORCID, Torcasio Roberta2, Valentino Ilenia2, Trapasso Francesco2, Viglietto Giuseppe2, Alcaro Stefano134ORCID, Costa Giosuè13ORCID, Amodio Nicola2
Affiliation:
1. Dipartimento di Scienze della Salute, Università “Magna Græcia” di Catanzaro, Campus “S. Venuta”, 88100 Catanzaro, Italy 2. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi “Magna Græcia” di Catanzaro, Campus “S. Venuta”, Viale Europa, 88100 Catanzaro, Italy 3. Net4Science Academic Spin-Off, Università “Magna Græcia” di Catanzaro, Campus “S. Venuta”, 88100 Catanzaro, Italy 4. Associazione CRISEA—Centro di Ricerca e Servizi Avanzati per l’Innovazione Rurale, Loc. Condoleo, 88055 Belcastro, Italy
Abstract
Polyphenols, an important class of natural products, are widely distributed in plant-based foods. These compounds are endowed with several biological activities and exert protective effects in various physiopathological contexts, including cancer. We herein investigated novel potential mechanisms of action of polyphenols, focusing on the proteasome, which has emerged as an attractive therapeutic target in cancers such as multiple myeloma. We carried out a structure-based virtual screening study using the DrugBank database as a repository of FDA-approved polyphenolic molecules. Starting from 86 polyphenolic compounds, based on the theoretical binding affinity and the interactions established with key residues of the chymotrypsin binding site, we selected 2 promising candidates, namely Hesperidin and Diosmin. The further assessment of the biologic activity highlighted, for the first time, the capability of these two molecules to inhibit the β5-proteasome activity and to exert anti-tumor activity against proteasome inhibitor-sensitive or resistant multiple myeloma cell lines.
Funder
Novel anticancer agents endowed with multi-targeting mechanism of action Italian Association for Cancer Research Italian Ministry of Health
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
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