Norharmane, a naturally occurring photosensitizer: photooxidation of 2´-deoxyguanosine-5´-monophosphate

M. MICAELA GONZÁLEZ; FEDERICO A. O. RASSE-SURIANI; SANTIAGO ROLDAN; ROSA ERRA-BALSELLS; FRANCO M. CABRERIZO

Sao Paulo

Congreso; Advanced School Sao Paulo (ESPCA) on Redox Processes in Biomedicine.; 2011

β-carbolines (βCs) are alkaloids belonging to a family of heterocyclic compounds showing in its structure the norharman moiety. βC alkaloids are present in a wide range of biological systems and play a variety of significant photo-dependent roles. These alkaloids are able to act as good photosensitizers. I.e., under UV-A irradiation, norharmane and harmane are able to induce chromosome damage in mammalian cells,[1] and to inactivate bacteria[2] and viruses[3]. More recently, we have demonstrated that photosensitized DNA relaxation by norharmane (upon UV-A excitation) takes place.[4] The later process involves, mainly, electron transfer reactions (i.e., Type I mechanism). In this work, we have studied the capability of norharmane to induce 2´-desoxyguanosine-5´-monophosphate (dGMP) photooxidation, in aqueous solution, upon UV-A (350 nm) excitation. The effect of pH was evaluated and the participation of several reactive oxygen species, such as hydroxyl radical (HO•), superoxide anion (O2•-) and singlet oxygen (1O2) was investigated. A strong dependence of the dGMP photosensitization on the pH was observed. The extent of the reaction was shown to be higher in the experiments performed at pH 4.7 than those performed at pH 10.2. Kinetic studies using D2O as a solvent revealed that 1O2 plays an important role in the photooxidation of dGMP (Type II mechanism). The chemical nature of the photoproducts formed upon photosensitization was characterized by mass spectrometry (ESI-MS and UV-MALDI-TOF-MS). These results suggest that the typical photoproduct 8-oxo-guanosine, among other products, is formed. [1] K. Shimoi, H. Kawabata, I. Tomita, Mutat. Res. 1992, 268, 287. [2] K. Shimoi, R. Miyamura, T. Mori, T. Todo, E. Ohtsuka, K. Wakabayashi, N. Kinae, Carcinogenesis 1996, 17, 1279. [3] J.B. Hudson, E.A. Graham, G.H.N. Towers, Photochem. Photobiol. 1986, 43, 21. [4] M. M. Gonzalez, M. Pellon-Maison, M. A. Ales-Gandolfo, M. R. Gonzalez-Baró, R. Erra-Balsells, F. M. Cabrerizo, Org. Biomol. Chem., 2010, 8, 2543.