title: UVA-induced effects of 2,6-disubstituted 4-anilinoquinazolines on cancer cell lines.
abstract: Five 2,6-substituted 4-anilinoquinazolines were evaluated for their ability to generate superoxide radical anion and singlet oxygen upon UVA irradiation and to induce cytotoxic/phototoxic effects on cancer cell lines L1210, HeLa and HT-29. The formation of radical intermediates, especially reactive oxygen species, upon UVA photoexcitation of the studied derivatives was monitored by indirect techniques of EPR spectroscopy. For all 4-anilinoquinazolines the photoinduced generation of superoxide radical anion was evidenced using spin trapping agent 5,5-dimethyl-1-pyrroline N-oxide, and the presence of (1)O2 was detected by the oxidation of 4-hydroxy-2,2,6,6-tetramethylpiperidine to the paramagnetic species 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxyl. The confirmed photoinduced activation of molecular oxygen via both Type I and Type II photooxidation mechanisms indicates potential phototoxic responses in cells. Biological results showed that derivatives I-V initiated different cytotoxic/phototoxic effects dependent on their concentration, time of treatment and the character of the cell line. UVA irradiation increased the cytotoxic activity of all tested 4-anilinoquinazoline derivatives. The highest cytotoxicity/phototoxicity on all tested cancer cells was induced by N,2-diphenyl-quinazolin-4-amine (derivative III). This most effective derivative emerged as the potent photosensitizer, which possesses a significant antiproliferative activity and DNA damage in L1210 cells increased by UVA irradiation. In addition derivative III induced programmed cell death in leukemia cells through mitochondrial/caspase 9/caspase 3-dependent pathway.
authors.affiliation: Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Jantová
authors.affiliation: Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Melušová
authors.affiliation: Institute of Management of the Slovak University of Technology in Bratislava, Vazovova 5, SK-812 43 Bratislava, Slovak Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pánik
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Brezová
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic. Electronic address: zuzana.barbierikova@stuba.sk.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Barbieriková
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004578:Electron Spin Resonance Spectroscopy; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010084:Oxidation-Reduction; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D017319:Photosensitizing Agents; D011799:Quinazolines; D013481:Superoxides; D026082:Singlet Oxygen; D053148:Caspase 3; D053453:Caspase 9
keywords: 4-Anilinoquinazolines; Apoptosis; Cytotoxic/phototoxic effects; EPR spectroscopy; Leukemia; Photoinduced processes; Spin trapping