title: Photochemical and photobiological studies on furoquinazolines as new psoralen analogs.
abstract: Linear (L) and angular (A) 4',5'-dimethylfuroquinazolines (FQZs) were synthesized and studied as furocoumarin analogs. These molecules proved to be photounstable with a photodegradation extent correlated to UVA light doses. Both compounds did intercalate inside the DNA double helix, but were not able to photobind DNA bases under UVA irradiation. This behavior was further rationalized through docking studies. The photosensitizing effects of these compounds were evaluated on Jurkat tumor cells and NCTC-2544 human keratinocytes, with and without antioxidants, to demonstrate the involvement of a photodynamic mechanism. Indeed, significant amounts of singlet oxygen and superoxide anion were generated in the presence of both compounds, that account for the oxidative damage induced to some isolated biological substrates (DNA, amino acids, proteins and lipids). Photophysical studies by use of a flash photolysis set up showed detectable triplet population and production of singlet reactive oxygen species for linear furoquinazoline, which can be responsible for the oxidation of biological substrates, and therefore can affect the cell proliferation.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. Electronic address: giorgia.miolo@unipd.it.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Miolo
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Salvador
authors.affiliation: Department of Chemistry, University of Perugia, via Elce di Sotto 8, 06123 Perugia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mazzoli
authors.affiliation: Department of Chemistry, University of Perugia, via Elce di Sotto 8, 06123 Perugia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Spalletti
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marzaro
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Chilin
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000737:chemistry*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D005663:Furans / Q000737:chemistry* / Q000633:toxicity; D011564:Furocoumarins / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D019169:Jurkat Cells; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008958:Models, Molecular; D010782:Photolysis / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000633:toxicity; D011799:Quinazolines / Q000737:chemistry* / Q000633:toxicity; D026082:Singlet Oxygen / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D005663:Furans; D011564:Furocoumarins; D017319:Photosensitizing Agents; D011799:Quinazolines; D013481:Superoxides; D026082:Singlet Oxygen; D004247:DNA
keywords: DNA intercalation; Furocoumarins; Furoquinazolines; Photobiological activity; Phototoxic activity