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

N.J. Wheate, R.I. Taleb, A.M. Krause-Heuer, J.R. Aldrich-Wright, V.J. Higgins, S. Wang

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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 -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.
Original languageEnglish
Pages (from-to)5055-5064
Number of pages9
JournalDalton Transactions
Volume2007
DOIs
Publication statusPublished - 2007

Keywords

  • anticancer complexes
  • molecular hosts
  • drug delivery vehicles
  • platinum
  • pharmacological sciences
  • biomedical sciences

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    Wheate, N. J., Taleb, R. I., Krause-Heuer, A. M., Aldrich-Wright, J. R., Higgins, V. J., & Wang, S. (2007). Novel platinum(II)-based anticancer complexes and molecular hosts as their drug delivery vehicles. Dalton Transactions, 2007, 5055-5064. https://doi.org/10.1039/b704973k