DNA‐binding affinity and nuclease activity of two cytotoxic copper terpyridine complexes |
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Authors: | Pengfei Shi Miaoxin Lin Jianhui Zhu Yangmiao Zhang Qin Jiang |
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Affiliation: | 1. Chemistry Department, Huaihai Institute of Technology, Lianyungang 222005, People's Republic of China;2. State Key Laboratory of Coordination Chemistry, Nanjing University, 210093 Nanjing, People's Republic of China |
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Abstract: | Two copper(II) terpyridine complexes, [Cu(atpy)(NO3)(H2O)](NO3) ? 3H2O ( 1 ) and [Cu(ttpy)(NO3)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 |
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Keywords: | Terpyridine‐Cu(II) Cytotoxicity DNA nuclease activity DNA‐binding affinity |
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