A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential Applications
The treatment of cancer represents one of the most significant challenges currently facing modern medicine. The search for new drugs that are effective in the treatment of patients is an ongoing endeavor. It is frequently the case that the molecular target of anticancer drugs is a DNA molecule. The...
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2024-11-01
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| author | Aleksandra Marciniak Edward Krzyżak Dominika Szkatuła Krystian Mazurkiewicz Aleksandra Kotynia |
| author_facet | Aleksandra Marciniak Edward Krzyżak Dominika Szkatuła Krystian Mazurkiewicz Aleksandra Kotynia |
| author_sort | Aleksandra Marciniak |
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| description | The treatment of cancer represents one of the most significant challenges currently facing modern medicine. The search for new drugs that are effective in the treatment of patients is an ongoing endeavor. It is frequently the case that the molecular target of anticancer drugs is a DNA molecule. The therapeutic effect of a drug is achieved by influencing the structure of a macromolecule or by inhibiting its function. Among the synthetic substances with potential anticancer effects, particular attention should be paid to phthalic acid imide derivatives. Three phthalimide derivatives are employed in the treatment of multiple myeloma: thalidomide, pomalidomide, and lenalidomide. Nevertheless, the search for new derivatives with a diverse range of biological activities is ongoing. In light of the above, the subject of our investigation is four non-toxic phthalic acid imide derivatives. The objective was to analyze the interaction of these compounds with DNA. The use of spectroscopic and in silico methods has enabled us to demonstrate that all of the tested analogs can act as ligands for deoxyribonucleic acid, forming non-covalent bonds with it. All four compounds tested interact with the ctDNA molecule, binding in its minor groove. The most stable complex is formed here between deoxyribonucleic acid and the C derivative, in which the -CF<sub>3</sub> group is attached to the benzene ring. What is interesting and important, the described mechanism of action is analogous to that observed between ctDNA and thalidomide, pomalidomide, and lenalidomide. |
| format | Article |
| id | doaj-art-738779bc36df437f8c9fd8bbd0601a85 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Molecules |
| spelling | doaj-art-738779bc36df437f8c9fd8bbd0601a852025-08-20T01:54:03ZengMDPI AGMolecules1420-30492024-11-012922542210.3390/molecules29225422A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential ApplicationsAleksandra Marciniak0Edward Krzyżak1Dominika Szkatuła2Krystian Mazurkiewicz3Aleksandra Kotynia4Department of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, PolandDepartment of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, Poland“Biomolecule” Student Science Club, Department of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, PolandDepartment of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, PolandThe treatment of cancer represents one of the most significant challenges currently facing modern medicine. The search for new drugs that are effective in the treatment of patients is an ongoing endeavor. It is frequently the case that the molecular target of anticancer drugs is a DNA molecule. The therapeutic effect of a drug is achieved by influencing the structure of a macromolecule or by inhibiting its function. Among the synthetic substances with potential anticancer effects, particular attention should be paid to phthalic acid imide derivatives. Three phthalimide derivatives are employed in the treatment of multiple myeloma: thalidomide, pomalidomide, and lenalidomide. Nevertheless, the search for new derivatives with a diverse range of biological activities is ongoing. In light of the above, the subject of our investigation is four non-toxic phthalic acid imide derivatives. The objective was to analyze the interaction of these compounds with DNA. The use of spectroscopic and in silico methods has enabled us to demonstrate that all of the tested analogs can act as ligands for deoxyribonucleic acid, forming non-covalent bonds with it. All four compounds tested interact with the ctDNA molecule, binding in its minor groove. The most stable complex is formed here between deoxyribonucleic acid and the C derivative, in which the -CF<sub>3</sub> group is attached to the benzene ring. What is interesting and important, the described mechanism of action is analogous to that observed between ctDNA and thalidomide, pomalidomide, and lenalidomide.https://www.mdpi.com/1420-3049/29/22/5422phthalimide analogspectroscopyUV-VisCDmolecular modelingDNA |
| spellingShingle | Aleksandra Marciniak Edward Krzyżak Dominika Szkatuła Krystian Mazurkiewicz Aleksandra Kotynia A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential Applications Molecules phthalimide analog spectroscopy UV-Vis CD molecular modeling DNA |
| title | A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential Applications |
| title_full | A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential Applications |
| title_fullStr | A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential Applications |
| title_full_unstemmed | A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential Applications |
| title_short | A Spectroscopic and In Silico Description of the Non-Covalent Interactions of Phthalic Acid Imide Derivatives with Deoxyribonucleic Acid—Insights into Their Binding Characteristics and Potential Applications |
| title_sort | spectroscopic and in silico description of the non covalent interactions of phthalic acid imide derivatives with deoxyribonucleic acid insights into their binding characteristics and potential applications |
| topic | phthalimide analog spectroscopy UV-Vis CD molecular modeling DNA |
| url | https://www.mdpi.com/1420-3049/29/22/5422 |
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