Cytotoxic activity, cell imaging and photocleavage of DNA induced by a Pt(II) cyclophane bearing 1,2 diamino ethane as a terminal ligand

Kumari, Niraj, Maurya, Brajesh Kumar, Koiri, Raj Kumar, Trigun, Surendar Kumar, Saripella, Srikrishna, Coogan, Michael and Mishra, Lallan 2011. Cytotoxic activity, cell imaging and photocleavage of DNA induced by a Pt(II) cyclophane bearing 1,2 diamino ethane as a terminal ligand. MedChemComm 2 (12) , pp. 1208-1216. 10.1039/c1md00159k

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Abstract

A PtII complex [{Pt(en)L}2]·4PF6 (Ptcyp) (LH2 = N,N′-bis(salicylidene)-p-phenylenediamine, en = 1,2-diamino ethane) shows high cytotoxicity against HeLa cells (IC50—11.5 μM) and against Dalton's lymphoma (DL) cells (IC50—0.65 nM); UV-vis titration of Ptcyp with calf thymus DNA (CT-DNA) demonstrated its DNA binding, which could be further quantified by competitive fluorescence titration of DNA, Ptcyp and ethidium bromide. Circular dichroism studies suggest that Ptcyp interacts with CT-DNA by intercalation in an aqueous medium containing a minimum amount of DMSO. Agarose gel electrophoresis showed that Ptcyp is able to convert a supercoiled pBR322 plasmid DNA into a nicked circular DNA in DMSO, but to a much lower extent in an aqueous medium. However, with UV irradiation, Ptcyp is able to cause concentration-dependent nicking of supercoiled DNA in an aqueous medium. These findings indicate the DNA binding and UV exposure-dependent DNA cleavage properties of Ptcyp. Cell imaging studies using the HeLa cell line carried out in the presence of Ptcyp represent one of the first examples of Pt complexes applied as fluorophores in cell imaging and strongly support its interaction with DNA.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Publisher:	RSC Publishing
ISSN:	2040-2503
Last Modified:	19 Mar 2016 22:28
URI:	https://orca.cardiff.ac.uk/id/eprint/17269

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