Lipophilic photosensitizers: Synthesis, properties and lipid peroxidation activity

MAURICIO S. BAPTISTA; JOSÉ LUIS FONSECA CASTRO; ALEXANDER GREER; ROSANGELA ITRI; HELENA C. JUNQUEIRA; MARIA JOSÉ SOSA; ANDRÉS H. THOMAS; MARIA NOEL URRUTIA; MARIANA VIGNONI; NILUKSHA WALALAWELA

Santos, São Paulo

Congreso; XLIV Congresso Anual da Sociedade Brasileira de Biofísica; 2019

Pteridines are naturally occurring heterocyclic compounds that can be found in different biological systems.1 Under UVA excitation (320-400 nm) pteridines can fluoresce, undergo photooxidation and generate reactive oxygen species, such as singlet oxygen and superoxide anion.2 In the presence of oxygen, pteridines act as photosensitizers through both type I and type II mechanism. Since they are mainly hydrophilic compounds and do not interact with biomembranes, new lipophilic pteridines derivatives were synthesized.3,4 Through a nucleophilic substitution reaction (SN2), decyl carbon chains were attached to different positions of the heterocyclic compound. Several pteridines were used as reactants, such as pterin, lumazine, 6-carboxypterin and pteroic acid. These new decyl derivatives have high calculated lipophilicity comparing to the reactants and have good binding constant values, which indicate an important interaction with lipid biomembranes. In addition, decyl derivatives have higher singlet oxygen quantum yield than the hydrophilic pteridines, and good photosensitizer activity.5 Therefore, a new series of lipophilic, photooxidatively active pterins has been found that can act as a photosensitizer in a hydrophobic environment.1. W. Pfleiderer (1993) Chemistry and Biology of Pteridines and Folates, Vol. 338, pp. 1?16. Plenum Press, New York.2. C. Lorente, A. H. Thomas (2006) Acc. Chem. Res. 39, 395?402.3. M. Vignoni, et.al. (2018) Mol. Pharm. 15, 798-8074. N. Walalawela, et.al. (2019) Photochem. Photobiol., in press5. M. Vignoni, et.al. (2018) Langmuir 34, 15578-15586.