Issue 43, 2007

Novel platinum(ii)-based anticancer complexes and molecular hosts as their drug delivery vehicles

Abstract

Platinum(II)-based DNA intercalators where the intercalating ligand is 1,10-phenanthroline or a phenanthroline derivative and where the ancillary ligand is either achiral (e.g. ethylenediamine) or chiral (e.g. diaminocyclohexane) show a range of cytotoxicities with a defined structure–activity relationship. The most cytotoxic are those that contain methylated-phenanthroline ligands and 1S,2S-diaminocyclohexane (S,S-dach) as the ancillary ligand. We have developed a new purification method using Sep-Pak® C-18 reverse phase columns, which means these metal complexes can be made faster and cheaper compared to published methods. Platinum(II)-based complexes containing imidazole, pyrrole and β-alanine subunits, that are capable of recognising specific DNA base-pair sequences have also been synthesised. These include linear or hairpin polyamide ligands that can recognise DNA sequences up to seven base-pairs in length and contain single platinum centres capable of forming monofunctional adducts with DNA. We have now synthesised and characterised, by 1H and 195Pt NMR, ESI-MS and elemental analysis, the first dinuclear platinum(II) DNA sequence selective agent. Finally, using 1H NMR we have examined the encapsulation of our platinum(II)-based DNA intercalators by cucurbit[6]uril (CB[6]). Encapsulation by CB[6] was found to not significantly change the cytotoxicity of five platinum(II)-based DNA intercalators, indicating it may have utility as a molecular carrier for improved drug delivery.

Graphical abstract: Novel platinum(ii)-based anticancer complexes and molecular hosts as their drug delivery vehicles

Supplementary files

Article information

Article type
Paper
Submitted
02 Apr. 2007
Accepted
03 Maijs 2007
First published
27 Sept. 2007

Dalton Trans., 2007, 5055-5064

Novel platinum(II)-based anticancer complexes and molecular hosts as their drug delivery vehicles

N. J. Wheate, R. I. Taleb, A. M. Krause-Heuer, R. L. Cook, S. Wang, V. J. Higgins and J. R. Aldrich-Wright, Dalton Trans., 2007, 5055 DOI: 10.1039/B704973K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements