INVESTIGADORES
CABRERIZO Franco Martin
congresos y reuniones científicas
Título:
Norharmane, a naturally occurring photosensitizer: photooxidation of 2´-deoxyguanosine-5´-monophosphate
Autor/es:
M. MICAELA GONZÁLEZ; FEDERICO A. O. RASSE-SURIANI; SANTIAGO ROLDAN; ROSA ERRA-BALSELLS; FRANCO M. CABRERIZO
Lugar:
Sao Paulo
Reunión:
Congreso; Advanced School Sao Paulo (ESPCA) on Redox Processes in Biomedicine.; 2011
Resumen:
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.