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Naphthoquinolizinium derivatives as a novel platform for DNA-binding and DNA-photodamaging chromophores

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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 ≈ 105 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.

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Acknowledgements

This work was generously financed by the Bundesministerium für Bildung und Forschung, the Deutsche Forschungsgemeinschaft, the Deutscher Akademischer Austauschdienst and CRUI (Vigoni programm) and the Fonds der Chemischen Industrie. H. I. thanks Prof. Waldemar Adam for generous support and encouragement. We thank Dr. Stefan Marquardt for help with the determination of 8-oxoGua and one referee for helpful comments.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Padova, via Marzolo 5, Italy

    Giampietro Viola, Milena Bressanini, Daniela Vedaldi & Francesco Dall‘Acqua

  2. Department of Biological Chemistry, University of Padova, via G. Colombo 3, Italy

    Nadia Gabellini

  3. Institute of Organic Chemistry, University of Würzburg, Am Hubland, Würzburg, Germany

    Milena Bressanini & Heiko Ihmels

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  1. Giampietro Viola
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  2. Milena Bressanini
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  5. Francesco Dall‘Acqua
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  6. Heiko Ihmels
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Correspondence to Giampietro Viola.

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Viola, G., Bressanini, M., Gabellini, N. et al. Naphthoquinolizinium derivatives as a novel platform for DNA-binding and DNA-photodamaging chromophores. Photochem Photobiol Sci 1, 882–889 (2002). https://doi.org/10.1039/B204275D

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