Structural Determinants of p53-Independence in Anticancer Ruthenium-Arene Schiff-Base Complexes

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Mun Juinn Chow
  • Daniel Yuan Qiang Wong
  • Giorgia Pastorin
  • Christian Gaiddon
  • Wee Han Ang

Detail(s)

Original languageEnglish
Pages (from-to)2543-2554
Journal / PublicationMolecular Pharmaceutics
Volume13
Issue number7
Online published13 May 2016
Publication statusPublished - 5 Jul 2016
Externally publishedYes

Abstract

p53 is a key tumor suppressor gene involved in key cellular processes and implicated in cancer therapy. However, it is inactivated in more than 50% of all cancers due to mutation or overexpression of its negative regulators. This leads to drug resistance and poor chemotherapeutic outcome as most clinical drugs act via a p53-dependent mechanism of action. An attractive strategy to circumvent this resistance would be to identify new anticancer drugs that act via p53-independent mode of action. In the present study, we identified 9 Ru (II)-Arene Schiff-base (RAS) complexes able to induce p53-independent cytotoxicity and discuss structural features that are required for their p53-independent activity. Increasing hydrophobicity led to an increase in cellular accumulation in cells with a corresponding increase in efficacy. We further showed that all nine complexes demonstrated p53-independent activity. This was despite significant differences in their physicochemical properties, suggesting that the iminoquinoline ligand, a common structural feature for all the complexes, is required for the p53-independent activity.

Research Area(s)

  • anticancer, p53-independent activity, ruthenium-arene Schiff-base complexes, structure-activity relationship studies

Citation Format(s)

Structural Determinants of p53-Independence in Anticancer Ruthenium-Arene Schiff-Base Complexes. / Chow, Mun Juinn; Babak, Maria V.; Wong, Daniel Yuan Qiang et al.
In: Molecular Pharmaceutics, Vol. 13, No. 7, 05.07.2016, p. 2543-2554.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review