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Synthesis, characterization, plasmid cleavage and cytotoxicity of cancer cells by a copper(II) complex of anthracenyl-terpyridine

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Title Synthesis, characterization, plasmid cleavage and cytotoxicity of cancer cells by a copper(II) complex of anthracenyl-terpyridine
 
Creator KUMAR, A
CHINTA, JP
AJAY, AK
BHAT, MK
RAO, CP
 
Subject STRAND DNA CLEAVAGE
HETEROCYCLIC BASES
CRYSTAL-STRUCTURE
ANTICANCER ACTIVITY
GOLD(I) COMPLEXES
BINDING
LIGANDS
ACID
1,10-PHENANTHROLINE
DERIVATIVES
 
Description Metallo-organic compounds are interesting to study for their antitumor activity and related applications. This paper deals with the syntheses, characterization, structure determination of a copper complex of anthracenyl terpyridine (1) and its plasmid cleavage and cytotoxicity towards different cancer cell lines. The complex binds CT-DNA through partial intercalation mode. The plasmid cleavage studies carried out using pBR322 and pUC18 resulted in the formation of all the three forms of the plasmid DNA. Plasmid cleavage studies carried out with a non-redoxable Zn(2+) complex (2) supported the role of the redox activity of copper in 1. The complex 1 showed remarkable antiproliferative activity against cancer cell lines, viz., cervical (HeLa, SiHa, CaSki), breast (MCF-7), liver (HepG2) and lung (H1299). A considerable lowering was observed in the IC(50) values of HPV-infected (viz., HeLa, SiHa, CaSki) vs. non-HPV-infected cell lines (MCF-7, HepG2, H1299). Antiproliferative activity of 1 was found to be much higher than the carboplatin when treated with the same cell lines. Incubation of the cells with 1 results in granular structures only with the HPV-infected cells and not with others as studied by phase contrast and fluorescence microscopy. The lower IC(50) value observed in case of 1 with HPV-infected cell lines may be correlated with the involvement of HPV oncoprotein. The role of HPV has been further augmented by transfecting the MCF-7 cells (originally not possessing HPV copy) with e6 oncoprotein cDNA. To our knowledge this is the first copper complex that causes cell death by interacting with HPV oncoprotein followed by exhibition of remarkable antiproliferative activity.
 
Publisher ROYAL SOC CHEMISTRY
 
Date 2012-06-26T09:27:18Z
2012-06-26T09:27:18Z
2011
 
Type Article
 
Identifier DALTON TRANSACTIONS,40(41)10865-10872
1477-9226
http://dx.doi.org/10.1039/c1dt10201j
http://dspace.library.iitb.ac.in/jspui/handle/100/14285
 
Language English