title: Naphthoquinolizinium derivatives as a novel platform for DNA-binding and DNA-photodamaging chromophores.
abstract: The association of the naphtho[1,2-b]quinolizinium bromide (5a) and naphtho[2,1-b]quinolizinium bromide (5b) with DNA and the propensity of these cationic arenes to damage DNA after UV-A irradiation have been studied. Spectrophotometric and fluorimetric titrations show that the two isomers 5a and 5b bind to DNA (K approximately 10(5) M(-1)). The highest affinity was observed for GC base pairs. The mode of binding was investigated by CD and LD spectroscopy. Whereas quinolizinium 5a exclusively intercalates in DNA, the isomer 5b exhibits a deviation from perfect intercalation into the double helix. Moreover, efficient DNA damage was observed on UV-A irradiation in the presence of the quinolizinium salts. Primer extension analysis indicates that the photocleavage takes place preferentially at guanine-rich regions.
authors.affiliation: Department of Pharmaceutical Sciences, via Marzolo 5, University of Padova, Italy. giampietro.viola.1@unipd.it
authors.forename: Giampietro
authors.initials: G
authors.lastname: Viola
authors.forename: Milena
authors.initials: M
authors.lastname: Bressanini
authors.forename: Nadia
authors.initials: N
authors.lastname: Gabellini
authors.forename: Daniela
authors.initials: D
authors.lastname: Vedaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Dall'Acqua
authors.forename: Heiko
authors.initials: H
authors.lastname: Ihmels
mesh_terms: D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism / Q000379:methods; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004249:DNA Damage; D005470:Fluorometry / Q000379:methods; D006147:Guanine / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry*; D007700:Kinetics; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010777:Photochemistry; D011807:Quinolizines / Q000737:chemistry*
chemical_list: D007364:Intercalating Agents; D011807:Quinolizines; D006147:Guanine; D004247:DNA