Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure-activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined...
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todo:paper_14770520_v11_n32_p5300_Vignoni2023-10-03T16:19:02Z Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines Vignoni, M. Rasse-Suriani, F.A.O. Butzbach, K. Erra-Balsells, R. Epe, B. Cabrerizo, F.M. Binding properties Carboline derivatives Cyclobutane pyrimidine dimers Deuterated solvents Photochemical mechanism Physiological pH Single-strand breaks Structure activity relationships Aromatic compounds Binding energy Energy transfer pH Photosensitizers Protonation Pyridine DNA 9 methyl beta carboline 9-methyl-beta-carboline calf thymus dna carboline derivative DNA photosensitizing agent virus DNA animal article bacteriophage cattle chemical structure chemistry DNA damage drug effect genetics ultraviolet radiation Animals Carbolines Cattle Corticoviridae DNA DNA Damage DNA, Viral Models, Molecular Photosensitizing Agents Ultraviolet Rays It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure-activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl- norharmane, 9-methyl-harmane and 9-methyl-harmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet-triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent.© 2013 The Royal Society of Chemistry. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_14770520_v11_n32_p5300_Vignoni |
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Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Binding properties Carboline derivatives Cyclobutane pyrimidine dimers Deuterated solvents Photochemical mechanism Physiological pH Single-strand breaks Structure activity relationships Aromatic compounds Binding energy Energy transfer pH Photosensitizers Protonation Pyridine DNA 9 methyl beta carboline 9-methyl-beta-carboline calf thymus dna carboline derivative DNA photosensitizing agent virus DNA animal article bacteriophage cattle chemical structure chemistry DNA damage drug effect genetics ultraviolet radiation Animals Carbolines Cattle Corticoviridae DNA DNA Damage DNA, Viral Models, Molecular Photosensitizing Agents Ultraviolet Rays |
| spellingShingle |
Binding properties Carboline derivatives Cyclobutane pyrimidine dimers Deuterated solvents Photochemical mechanism Physiological pH Single-strand breaks Structure activity relationships Aromatic compounds Binding energy Energy transfer pH Photosensitizers Protonation Pyridine DNA 9 methyl beta carboline 9-methyl-beta-carboline calf thymus dna carboline derivative DNA photosensitizing agent virus DNA animal article bacteriophage cattle chemical structure chemistry DNA damage drug effect genetics ultraviolet radiation Animals Carbolines Cattle Corticoviridae DNA DNA Damage DNA, Viral Models, Molecular Photosensitizing Agents Ultraviolet Rays Vignoni, M. Rasse-Suriani, F.A.O. Butzbach, K. Erra-Balsells, R. Epe, B. Cabrerizo, F.M. Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines |
| topic_facet |
Binding properties Carboline derivatives Cyclobutane pyrimidine dimers Deuterated solvents Photochemical mechanism Physiological pH Single-strand breaks Structure activity relationships Aromatic compounds Binding energy Energy transfer pH Photosensitizers Protonation Pyridine DNA 9 methyl beta carboline 9-methyl-beta-carboline calf thymus dna carboline derivative DNA photosensitizing agent virus DNA animal article bacteriophage cattle chemical structure chemistry DNA damage drug effect genetics ultraviolet radiation Animals Carbolines Cattle Corticoviridae DNA DNA Damage DNA, Viral Models, Molecular Photosensitizing Agents Ultraviolet Rays |
| description |
It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure-activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl- norharmane, 9-methyl-harmane and 9-methyl-harmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet-triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent.© 2013 The Royal Society of Chemistry. |
| format |
JOUR |
| author |
Vignoni, M. Rasse-Suriani, F.A.O. Butzbach, K. Erra-Balsells, R. Epe, B. Cabrerizo, F.M. |
| author_facet |
Vignoni, M. Rasse-Suriani, F.A.O. Butzbach, K. Erra-Balsells, R. Epe, B. Cabrerizo, F.M. |
| author_sort |
Vignoni, M. |
| title |
Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines |
| title_short |
Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines |
| title_full |
Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines |
| title_fullStr |
Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines |
| title_full_unstemmed |
Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines |
| title_sort |
mechanisms of dna damage by photoexcited 9-methyl-β-carbolines |
| url |
http://hdl.handle.net/20.500.12110/paper_14770520_v11_n32_p5300_Vignoni |
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