DNA binding studies and cytotoxicity of a dinuclear PtII diazapyrenium-based metallo-supramolecular rectangular box

Research output: Contribution to journalArticle

Authors

  • Víctor Blanco
  • Lenka Zerzankova
  • Aron F. Westendorf
  • Carlos Peinador
  • José M. Quintela
  • Patrick J. Bednarski
  • Giampaolo Barone

Colleges, School and Institutes

External organisations

  • Dip. di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO)
  • Sezione di Chimica Farmaceutica e Biologica
  • Dipartimento di Scienze e Tecnologie Biologiche Ed Ambientali
  • University of Salento
  • University of A Coruña
  • Institute of Biophysics of the Academy of Sciences of the Czech Republic
  • University of Greifswald

Abstract

The interaction with native DNA of a 2,7-diazapyrenium-based ligand 1 and its PtII rectangular metallacycle 2 is explored through circular and linear dichroism and fluorescence spectroscopies. The metal-free ligand 1 binds through intercalation, with a binding constant of approximately 5 × 105a M-1, whereas the metallacycle 2 binds and bends the DNA with a binding constant of 7 × 106a M-1. PCR assays show that metallo-supramolecular box 2 interferes with DNA transactions in vitro whereas the intercalator 1 does not. The metallacycle is active against four human cancer cell lines, with IC50 values ranging between 3.1 and 19.μ M and shows similar levels of efficacy, but a different spectrum of activity, to cisplatin. Boxed in: Supramolecular boxes bind DNA, prevent DNA transactions and inhibit growth of cancer cells. The interaction of a 2,7-diazapyrenium-based ligand and its PtII rectangular metallacycle with native DNA (see scheme) was explored. The metallacycle is active against four human cancer cell lines, and shows similar levels of efficacy, but a different spectrum of activity, to cisplatin.

Details

Original languageEnglish
Pages (from-to)10983-10990
Number of pages8
JournalChemistry - A European Journal
Volume18
Issue number35
Publication statusPublished - 27 Aug 2012

Keywords

  • cytotoxicity, metallodrugs, noncovalent DNA binding, Pt rectangular box, supramolecular chemistry

ASJC Scopus subject areas