In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib
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Published:2023-04-06
Issue:7
Volume:28
Page:3277
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Bunea Mihaela-Cristina1ORCID,
Enache Teodor Adrian1ORCID,
Diculescu Victor Constantin1ORCID
Affiliation:
1. National Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, Romania
Abstract
Bortezomib is an inhibitor of proteasomes and an anti-cancer drug. Although bortezomib is considered a safe drug, as confirmed by cytotoxicity assays, recent reports highlighted the possibility of interaction between bortezomib and cellular components, with detrimental long-term effects. The evaluation of the interaction between bortezomib and dsDNA was investigated in bulk solution and using a dsDNA electrochemical biosensor. The binding of bortezomib to dsDNA involved its electroactive centers and led to small morphological modifications in the dsDNA double helix, which were electrochemically identified through changes in the guanine and adenine residue oxidation peaks and confirmed by electrophoretic and spectrophotometric measurements. The redox product of bortezomib amino group oxidation was electrochemically generated in situ on the surface of the dsDNA electrochemical biosensor. The redox product of bortezomib was shown to interact primarily with guanine residues, preventing their oxidation and leading to the formation of bortezomib–guanine adducts, which was confirmed by control experiments with polyhomonucleotides electrochemical biosensors and mass spectrometry. An interaction mechanism between dsDNA and bortezomib is proposed, and the formation of the bortezomib redox product–guanine adduct explained.
Funder
Romanian Executive Agency for Higher Education, Research, Development and Innovation Funding
Romanian Ministry of Research, Innovation and Digitalization
Core Program of the National Institute of Materials Physics
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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