TY - JOUR
T1 - Redox-active and DNA-binding coordination complexes of clotrimazole
AU - Betanzos-Lara, Soledad
AU - Chmel, Nikola P.
AU - Zimmerman, Matthew T.
AU - Barrón-Sosa, Lidia R.
AU - Garino, Claudio
AU - Salassa, Luca
AU - Rodger, Alison
AU - Brumaghim, Julia L.
AU - Gracia-Mora, Isabel
AU - Barba-Behrens, Norah
PY - 2015/2/28
Y1 - 2015/2/28
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=84922826677&partnerID=8YFLogxK
U2 - 10.1039/c4dt02883j
DO - 10.1039/c4dt02883j
M3 - Article
C2 - 25561277
AN - SCOPUS:84922826677
SN - 1477-9226
VL - 44
SP - 3673
EP - 3685
JO - Dalton Transactions
JF - Dalton Transactions
IS - 8
ER -