Issue 32, 2013

Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines

Abstract

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.

Graphical abstract: Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines

Article information

Article type
Paper
Submitted
15 Feb 2013
Accepted
18 Jun 2013
First published
18 Jun 2013

Org. Biomol. Chem., 2013,11, 5300-5309

Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines

M. Vignoni, F. A. O. Rasse-Suriani, K. Butzbach, R. Erra-Balsells, B. Epe and F. M. Cabrerizo, Org. Biomol. Chem., 2013, 11, 5300 DOI: 10.1039/C3OB40344K

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