In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib
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 evaluat...
| প্রধান লেখক: | , , |
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| বিন্যাস: | প্রবন্ধ |
| ভাষা: | English |
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MDPI AG
2023-04-01
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| মালা: | Molecules |
| বিষয়গুলি: | |
| অনলাইন ব্যবহার করুন: | https://www.mdpi.com/1420-3049/28/7/3277 |
| _version_ | 1827746627037691904 |
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| author | Mihaela-Cristina Bunea Teodor Adrian Enache Victor Constantin Diculescu |
| author_facet | Mihaela-Cristina Bunea Teodor Adrian Enache Victor Constantin Diculescu |
| author_sort | Mihaela-Cristina Bunea |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:28:58Z |
| format | Article |
| id | doaj.art-a3fd4d6e9cc74d59ac1c9d5d8425d6c5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T05:28:58Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a3fd4d6e9cc74d59ac1c9d5d8425d6c52023-11-17T17:16:08ZengMDPI AGMolecules1420-30492023-04-01287327710.3390/molecules28073277In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug BortezomibMihaela-Cristina Bunea0Teodor Adrian Enache1Victor Constantin Diculescu2National Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, RomaniaNational Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, RomaniaNational Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, RomaniaBortezomib 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.https://www.mdpi.com/1420-3049/28/7/3277bortezomibredox productsDNAinteractiondsDNA electrochemical biosensor |
| spellingShingle | Mihaela-Cristina Bunea Teodor Adrian Enache Victor Constantin Diculescu In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib Molecules bortezomib redox products DNA interaction dsDNA electrochemical biosensor |
| title | In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib |
| title_full | In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib |
| title_fullStr | In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib |
| title_full_unstemmed | In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib |
| title_short | In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib |
| title_sort | in situ electrochemical evaluation of the interaction of dsdna with the proteasome inhibitor anticancer drug bortezomib |
| topic | bortezomib redox products DNA interaction dsDNA electrochemical biosensor |
| url | https://www.mdpi.com/1420-3049/28/7/3277 |
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