Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells
A set of arylazo sulfones, known to undergo N–S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probab...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/1834 |
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| author | Chrysoula Mikra Achilleas Mitrakas Virginia Ghizzani Katerina R. Katsani Maria Koffa Michael Koukourakis George Psomas Stefano Protti Maurizio Fagnoni Konstantina C. Fylaktakidou |
| author_facet | Chrysoula Mikra Achilleas Mitrakas Virginia Ghizzani Katerina R. Katsani Maria Koffa Michael Koukourakis George Psomas Stefano Protti Maurizio Fagnoni Konstantina C. Fylaktakidou |
| author_sort | Chrysoula Mikra |
| collection | DOAJ |
| description | A set of arylazo sulfones, known to undergo N–S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probably due to DNA intercalation) was analyzed by means of molecular docking “in silico” calculations that pointed out polar contacts, mainly via the sulfonyl moiety. Incubation with plasmid pBluescript KS II revealed DNA cleavage that has been studied over time and concentration. UV-A irradiation considerably improved DNA damage for most of the compounds, whereas under visible light the effect was slightly lower. Moving to in vitro experiments, irradiation was found to slightly enhance the death of the cells in the majority of the compounds. Naphthylazosulfone <b>1</b> showed photo-disruptive effect under UV-A irradiation (IC<sub>50</sub> ~13 μΜ) followed by derivatives <b>14</b> and <b>17</b> (IC<sub>50</sub> ~100 μΜ). Those compounds were irradiated in the presence of two non-cancer cell lines and were found equally toxic only upon irradiation and not in the dark. The temporal and spatial control of light, therefore, might provide a chance for these novel scaffolds to be useful for the development of phototoxic pharmaceuticals. |
| first_indexed | 2024-03-11T09:43:55Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:43:55Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6863ad098aa34952b915ae9db8f79afb2023-11-16T16:48:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243183410.3390/ijms24031834Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer CellsChrysoula Mikra0Achilleas Mitrakas1Virginia Ghizzani2Katerina R. Katsani3Maria Koffa4Michael Koukourakis5George Psomas6Stefano Protti7Maurizio Fagnoni8Konstantina C. Fylaktakidou9Laboratory of Organic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceLaboratory of Cellular Biology and Cell Cycle, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, GreecePhotoGreen Lab, Department of Chemistry, University of Pavia, V. Le Taramelli 12, 27100 Pavia, ItalyLaboratory of Biochemistry and Molecular Virology, Molecular Biology and Genetics Department, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, GreeceLaboratory of Cellular Biology and Cell Cycle, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, GreeceDepartment of Radiotherapy and Oncology, Democritus University of Thrace, University General Hospital of Alexandroupolis, 68100 Alexandroupolis, GreeceLaboratory of Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreecePhotoGreen Lab, Department of Chemistry, University of Pavia, V. Le Taramelli 12, 27100 Pavia, ItalyPhotoGreen Lab, Department of Chemistry, University of Pavia, V. Le Taramelli 12, 27100 Pavia, ItalyLaboratory of Organic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceA set of arylazo sulfones, known to undergo N–S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probably due to DNA intercalation) was analyzed by means of molecular docking “in silico” calculations that pointed out polar contacts, mainly via the sulfonyl moiety. Incubation with plasmid pBluescript KS II revealed DNA cleavage that has been studied over time and concentration. UV-A irradiation considerably improved DNA damage for most of the compounds, whereas under visible light the effect was slightly lower. Moving to in vitro experiments, irradiation was found to slightly enhance the death of the cells in the majority of the compounds. Naphthylazosulfone <b>1</b> showed photo-disruptive effect under UV-A irradiation (IC<sub>50</sub> ~13 μΜ) followed by derivatives <b>14</b> and <b>17</b> (IC<sub>50</sub> ~100 μΜ). Those compounds were irradiated in the presence of two non-cancer cell lines and were found equally toxic only upon irradiation and not in the dark. The temporal and spatial control of light, therefore, might provide a chance for these novel scaffolds to be useful for the development of phototoxic pharmaceuticals.https://www.mdpi.com/1422-0067/24/3/1834arylazo sulfonesDNA bindingDNA cleavageDNA photocleavageA375 melanoma cellsmolecular docking |
| spellingShingle | Chrysoula Mikra Achilleas Mitrakas Virginia Ghizzani Katerina R. Katsani Maria Koffa Michael Koukourakis George Psomas Stefano Protti Maurizio Fagnoni Konstantina C. Fylaktakidou Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells International Journal of Molecular Sciences arylazo sulfones DNA binding DNA cleavage DNA photocleavage A375 melanoma cells molecular docking |
| title | Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells |
| title_full | Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells |
| title_fullStr | Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells |
| title_full_unstemmed | Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells |
| title_short | Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells |
| title_sort | effect of arylazo sulfones on dna binding cleavage photocleavage molecular docking studies and interaction with a375 melanoma and non cancer cells |
| topic | arylazo sulfones DNA binding DNA cleavage DNA photocleavage A375 melanoma cells molecular docking |
| url | https://www.mdpi.com/1422-0067/24/3/1834 |
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