期刊
DALTON TRANSACTIONS
卷 42, 期 48, 页码 16749-16761出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3dt51209f
关键词
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资金
- Department of Biotechnology [BT/PR6345/Med/14/784/2005]
- DST-PURSE Programme
- DRS-1 (SAP) from UGC, New Delhi, India
The chiral monometallic Cu-II (1) and Zn-II (2) and heterobimetallic Cu-II-Sn-IV and Zn-II-Sn-IV complexes with tridentate chiral Schiff base -ONO-ligand in the presence of nitrogen donor heterocyclic ligand imidazole; were prepared and characterized by various physico-chemical and spectroscopic methods. Preliminary complex-DNA interaction studies employing optical methods revealed that 3 displayed a higher propensity towards the drug target DNA double helix and recommended predominantly an electrostatic mode of interaction as well as a groove binding affinity of the complex with CT-DNA. This was quantified by K-b and K-SV values of complexes 1-4, which demonstrated a multifold increase in complex 3 binding to CT DNA and clearly demonstrates its potency to act as a chemotherapeutic agent. Furthermore, the gel electrophoretic patterns of supercoiled pBR322 DNA with varying concentrations of complex 3 exhibits the ability to cleave DNA and follow a freely diffusible radical mechanism. The antiproliferative effects of complex 3 on human hepatoma cancer cells (Huh7) was investigated. Human Topo I inhibition assay by complex 3 was performed and results confirmed significantly good activity at lower concentrations than some of the classical Topo I inhibitors. Additionally, complex 3 was investigated for the expression of MMP-2 and TGF-beta by real time PCR. The cellular uptake of complex 3 by HeLa cells was studied by confocal microscopy.
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