Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Cytotoxic activity, cell imaging and photocleavage of DNA induced by a Pt(II) cyclophane bearing 1,2 diamino ethane as a terminal ligand
AU - Coogan, Michael
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
U2 - 10.1039/C1MD00159K
DO - 10.1039/C1MD00159K
M3 - Journal article
VL - 2
SP - 1208
EP - 1216
JO - MedChemComm
JF - MedChemComm
SN - 2040-2511
IS - 12
ER -