β-diketonate versus β-ketoiminate: the importance of a ferrocenyl moiety on improving the anticancer potency

Matthew Allison, Daniel Wilson, Christopher M Pask, Patrick C McGowan, Rianne M Lord

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Abstract

Herein we present a library of fully characterized beta-diketonate and beta-ketoiminate compounds that are functionalized with a ferrocenyl moiety. Their cytotoxic potential has been determined by screening against human breast adenocarcinomas (MCF-7 and MDA-MB-231), human colorectal carcinoma p53 wild type (HCT116 p53(+/+)) and normal human prostate (PNT2) cell lines. The ferrocenyl beta-diketonate compounds are more than 18 times more cytotoxic than the ferrocenyl beta-ketoiminate analogues. Against MCF-7, compounds functionalized at the meta position are up to nine times more cytotoxic than when functionalized at the para position. The ferrocenyl beta-diketonate compounds have increased selectivity towards MCF-7 and MDA-MB-231, with several complexes having selectivity index (SI) values that are more than nine times (MCF-7) and more than six times (MDA-MB-231) that of carboplatin. The stability of these compounds in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) has been assessed by NMR spectroscopy and mass spectrometry studies, and the compounds show no oxidation of the iron center from Fe-II to Fe-III. Cytotoxicity screening was performed in both DMSO and DMF, with no significant differences observedin their potency.

Original languageEnglish
Pages (from-to)1988-1996
Number of pages9
JournalChemBioChem
Volume21
Issue number14
Early online date16 Mar 2020
DOIs
Publication statusPublished - 16 Jul 2020

Keywords

  • CANCER
  • COMPLEXES
  • CYTOTOXICITY
  • EQUILIBRIUM
  • ESTROGEN-RECEPTOR MODULATORS
  • HYDROXYTAMOXIFEN
  • LIPID NANOCAPSULES
  • MECHANISMS
  • OXIDATION
  • PLATINUM
  • beta-diketonate ligands
  • beta-ketoiminate ligands
  • bioinorganic chemistry
  • cancer
  • ferrocenyl compounds

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