Photosensitizing properties of lumazine

M. PAULA DENOFRIO; SONJA HATZ; CAROLINA LORENTE; ANDRÉS H. THOMAS; FRANCO M. CABRERIZO; PETER R. OGILBY

Cubatao/Santos, SP., Brasil

Congreso; IX Encuentro Latinoamericano de Fotoquímica y Fotobiología (IX ELAFOT); 2008

Pteridines are heterocyclic compounds widespread in biological systems, participating in relevant biological functions. The participation of these molecules in different photobiological processes has been suggested or demonstrated in past decades, and interest in the photophysical, photochemical and photosensitizing properties of this group of compounds has subsequently increased. (1-4) Recently, an in vitro study of the photochemistry of Lumazine (Lum), a pteridine derivative, has been performed.(5) Briefly, this compound has a moderate solubility in H2O and is a very good singlet oxygen (1O2) sensitizer in this medium upon excitation with UV-A radiation (FD= 0.44 at pH=5.5). In addition, it is quite photostable (Fdeg= 2x10-4 at pH=5.5). These properties make Lum a potential sensitizer to be used in biological systems. In order to assess the photosensitizing capability of Lum, we have performed experiments using biomolecules (2’-deoxyguanosine 5’-monophosphate (dGMP)) and a cell line derived from cervical cancer cells (HeLa) as targets.             Air-equilibrated aqueous solutions containing dGMP and Lum were irradiated at 350 nm. Under these conditions, a fast consumption of dGMP was observed, whereas the concentration of Lum did not change. Results obtained show Lum is able to photoinduce oxidation of dGMP. In experiments performed using HeLa cells incubated in the presence of Lum, the study of the cell extract by fluorescence spectroscopy suggest that Lum uptake occurred. After irradiation with UV-A light, analysis with Rhodamine 123 and Trypan Blue assays showed a decrease in the viability of the Lum-treated HeLa cells, whereas this effect was not observed in the controls.       (1) Lorente, C.; Thomas, A. H., Acc. Chem. Res., (2006) 39, 395-402. (2) Gabriela Petroselli, M. Laura Dantola, Franco M. Cabrerizo, Alberto L. Capparelli, Carolina Lorente, Esther Oliveros and Andres H. Thomas, J. Am. Chem. Soc. (2008), 130, 3001-3011. (3) Petroselli, G.; Erra-Balsells, R.; Cabrerizo, F. M.; Lorente, C.; Capparelli, A. L.; Braun, A. M.; Oliveros, E.; Thomas, A. H. Org. Biomol. Chem. (2007), 5, 2792-2799. (4) Ito, K.; Kawanishi, S. Biochemistry (1997), 36, 1774-1781. (5) M. Paula Denofrio, A.H. Thomas, A.M. Braun, E. Oliveros, C. Lorente, J. Photochem. Photobiol. A: Chem. (2008), doi:10.1016/j.jphotochem.2008.08.003.