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DNA‐binding affinity and nuclease activity of two cytotoxic copper terpyridine complexes
Author(s) -
Shi Pengfei,
Lin Miaoxin,
Zhu Jianhui,
Zhang Yangmiao,
Jiang Qin
Publication year - 2009
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20292
Subject(s) - terpyridine , chemistry , dna , nuclease , hela , cytotoxicity , cisplatin , puc19 , stereochemistry , biochemistry , cell , biology , in vitro , plasmid , metal , genetics , organic chemistry , chemotherapy
Abstract Two copper(II) terpyridine complexes, [Cu(atpy)(NO 3 )(H 2 O)](NO 3 ) ⋅ 3H 2 O ( 1 ) and [Cu(ttpy)(NO 3 ) 2 ] ( 2 ) (atpy = 4′‐ p ‐N9‐adeninylmethyl‐phenyl‐2,2′:6,2″‐terpyridine; ttpy = 4′‐ p ‐tolyl‐2,2′:6,2″‐terpyridine) exhibited high cytotoxicity, with average ten times more potency than cisplatin against the human cervix carcinoma cell line (HeLa), the human liver carcinoma cell line (HepG2), the human galactophore carcinoma cell line (MCF7), and the human prostate carcinoma cell line (PC‐3). The cytotoxicity of the complex 1 was lower than that of the complex 2 . Both complexes showed more efficient oxidative DNA cleavage activity under irradiation with UV light at 260 nm than in the presence of ascorbic acid. Especially, complex 1 exhibited evident photoinduced double‐stranded DNA cleavage activity. The preliminary mechanism experiments revealed that hydrogen peroxide was involved in the oxidative DNA damage induced by both complexes. From the absorption titration data, the DNA‐binding affinity of the complexes with surpersoiled plasmid pUC19 DNA, polydAdT, and polydGdC was calculated and complex 2 showed higher binding affinity than complex 1 with all these substrates. The DNA cleavage ability and DNA‐binding affinity of both complexes depended on the substituent group on the terpyrdine ligands. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:295–302, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20292