Picture of wind turbine against blue sky

Open Access research with a real impact...

The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

The Energy Systems Research Unit (ESRU) within Strathclyde's Department of Mechanical and Aerospace Engineering is producing Open Access research that can help society deploy and optimise renewable energy systems, such as wind turbine technology.

Explore wind turbine research in Strathprints

Explore all of Strathclyde's Open Access research content

Studies into the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells

Krause-Heuer, A.M. and Grunert, R. and Kuhne, S. and Maruszak, M. and Wheate, N.J. and Le Pevelen, D. and Boag, L.R. and Fisher, D.M. (2009) Studies into the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells. Journal of Medicinal Chemistry, 52 (17). pp. 5474-5484. ISSN 0022-2623

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

We have examined the biological activity of 12 platinum(II)-based DNA intercalators of the type [Pt(IL)(AL)]2+, where IL is an intercalating ligand (1,10-phenanthroline or a methylated derivative) and AL is an ancillary ligand (diaminocyclohexane, diphenylethylenediamine or 1,2-bis(4-fluorophenyl)-1,2-ethylenediamine). The chiral compounds (1−9) and the racemic compounds (10−12) were tested against a panel of human cancer cell lines, with a number of complexes displaying activity significantly greater than that of cisplatin (up to 100-fold increase in activity in the A-427 cell line). The activity of the complexes containing diphenylethylenediamine (8 and 9) and 1,2-bis(4-fluorophenyl)-1,2-ethylenediamine (10−12) was significantly lower compared to the complexes containing diaminocyclohexane (1−7). Further in vitro testing, such as DNA unwinding, competition assays, and DNase 1 footprinting, was conducted on the most active compound (5) and its enantiomer (6) to provide information about the mechanism of action. These complexes display activity in cisplatin resistant cell lines, have higher cellular uptake than cisplatin, and do not activate caspase-3 as cisplatin does, indicating that these complexes exhibit a different mechanism of action.