Issue 48, 2013

Chiral heterobimetallic complexes targeting human DNA-topoisomerase Iα

Abstract

The chiral monometallic CuII (1) and ZnII (2) and heterobimetallic CuII–SnIV and ZnII–SnIV 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 Kb and KSV 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-β by real time PCR. The cellular uptake of complex 3 by HeLa cells was studied by confocal microscopy.

Graphical abstract: Chiral heterobimetallic complexes targeting human DNA-topoisomerase Iα

Article information

Article type
Paper
Submitted
08 May 2013
Accepted
29 Aug 2013
First published
30 Aug 2013

Dalton Trans., 2013,42, 16749-16761

Chiral heterobimetallic complexes targeting human DNA-topoisomerase Iα

S. Tabassum, A. Asim, R. A. Khan, Z. Hussain, S. Srivastav, S. Srikrishna and F. Arjmand, Dalton Trans., 2013, 42, 16749 DOI: 10.1039/C3DT51209F

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