NDLI: Redox-active and DNA-binding coordination complexes of clotrimazole

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chmel, Nikola P. Gracia-mora, Isabel Barrón-sosa, Lidia R. Rodger, Alison Betanzos-lara, Soledad Zimmerman, Matthew T. Garino, Claudio Salassa, Luca Brumaghim, Julia L. Barba-behrens, Norah
Description	Author Affiliation: Betanzos-Lara S ( Departamento de Química Inorgánica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, México, D.F. 04510, Mexico. norah@unam.mx.)
Abstract	DNA interactions of anticancer mononuclear $Cu^{2+},$ $Co^{2+},$ $Zn^{2+},$ and $Ni^{2+}$ complexes with the biologically active ligand clotrimazole (clotri) are reported. To fully characterize DNA binding modes for these complexes of the formulae $[M(clotri)_{2}Cl_{2}]·nH_{2}O$ (1–4), $[M(clotri)_{2}Br_{2}]·nH_{2}O$ (5,6), $[M(clotri)_{3}NO_{3}]NO_{3}·nH_{2}O$ (9), and $[M(clotri)_{3}(NO_{3})_{2}]$ (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 $Cu^{2+}$ 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.
ISSN	14779226
Issue Number	8
Volume Number	44
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-02-28
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Clotrimazole Chemistry Coordination Complexes DNA Metals Apoptosis Drug Effects Circular Dichroism Cobalt Chemical Synthesis Toxicity Copper Crystallography, X-Ray Metabolism DNA Damage HeLa Cells Humans Microscopy, Atomic Force Molecular Conformation Nickel Nucleic Acid Denaturation Oxidation-Reduction Ultraviolet Rays Zinc Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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