Phosphate diester cleavage, dna interaction and cytotoxic activity of a bimetallic bis(1,4,7-triazacyclononane) zinc complex
Montagner, Diego Gandin, Valentina Marzano, Cristina Erxleben, Andrea
Montagner, Diego
Gandin, Valentina
Marzano, Cristina
Erxleben, Andrea
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Publication Date
2014-06-24
Type
Article
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Montagner, Diego; Gandin, Valentina; Marzano, Cristina; Erxleben, Andrea (2014). Phosphate diester cleavage, dna interaction and cytotoxic activity of a bimetallic bis(1,4,7-triazacyclononane) zinc complex. European Journal of Inorganic Chemistry (25), 4084-4092
Abstract
The dinuclear zinc complex [Zn-2{bcmp(-H)}(mu-Cl)](ClO4)(2)center dot H2O {bcmp = 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol} has been synthesized and structurally characterized. The DNA binding affinity was assessed by ethidium bromide fluorescence quenching experiments. The complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration. Mechanistic studies were carried out using the DNA and RNA models bis(2,4-dinitrophenyl) phosphate (BDNPP) and 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). A detailed kinetic analysis suggested that the bridging OH group of the solution species [Zn-2{bcmp(-H)}(mu-OH)](2+) acts as the nucleophile in the hydrolysis of BDNPP, while in the case of HPNP, the bridging OH group acts as a general base and seems to shift to a terminal position upon substrate coordination. Finally, the cytotoxicity profile of the dinuclear zinc(II) complex was assessed. The complex showed promising in vitro antitumour activity against pancreatic and lung cancers cell lines.
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Publisher
Wiley-Blackwell
Publisher DOI
10.1002/ejic.201402319
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Attribution-NonCommercial-NoDerivs 3.0 Ireland