Redox-active and DNA-binding coordination complexes of clotrimazole

Soledad Betanzos-Lara, Nikola P. Chmel, Matthew T. Zimmerman, Lidia R. Barrón-Sosa, Claudio Garino, Luca Salassa, Alison Rodger, Julia L. Brumaghim, Isabel Gracia-Mora, Norah Barba-Behrens*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

DNA interactions of anticancer mononuclear Cu2+, Co2+, Zn2+, and Ni2+ complexes with the biologically active ligand clotrimazole (clotri) are reported. To fully characterize DNA binding modes for these complexes of the formulae [M(clotri)2Cl2]·nH2O (1-4), [M(clotri)2Br2]·nH2O (5,6), [M(clotri)3NO3]NO3·nH2O (9), and [M(clotri)3(NO3)2] (10), circular dichroism (CD) and linear dichroism (LD) spectroscopy, UV melting experiments, atomic force microscopy (AFM) and ethidium bromide (EtBr) displacement methods were used. Results indicate mixed electrostatic interactions, possibly through groove binding, that result in accretion and coiling of DNA. Electrochemical studies indicate that the Cu2+ complex 9 readily reduces to the reactive-oxygen-species-generating Cu+, which oxidatively damages DNA. There is a subtle correlation between logP values, calculated electrostatic potentials, and cytotoxicity of the complexes. The extent of cell-nucleus DNA-metal adduct formation in the HeLa cervix-uterine carcinoma cell line does not necessarily correlate with cytotoxicity, indicating that the nature of DNA lesions may be crucial to activity. This journal is

Original languageEnglish
Pages (from-to)3673-3685
Number of pages13
JournalDalton Transactions
Volume44
Issue number8
DOIs
Publication statusPublished - 28 Feb 2015
Externally publishedYes

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