Structure-activity relationships of anticancer ruthenium(II) complexes with substituted hydroxyquinolines

Dmytro Havrylyuk, Brock S. Howerton, Leona Nease, Sean Parkin, David K. Heidary, Edith C. Glazer

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


8-Hydroxyquinolines (HQ), including clioquinol, possess cytotoxic properties and are widely used as ligands for metal-based anticancer drug research. The number and identity of substituents on the HQ can have a profound effect on activity for a variety of inorganic compounds. Ruthenium complexes of HQ exhibit radically improved potencies, and operate by a new, currently unknown, mechanism of action. To define structure-activity relationships (SAR), a family of 22 Ru(II) coordination complexes containing mono-, di- and tri-substituted hydroxyquinoline ligands were synthesized and their biological activity evaluated. The complexes exhibited promising cytotoxic activity against a cancer cell line, and the SAR data revealed the 2- and 7-positions as key sites for the incorporation of halogens to improve potency. The Ru(II) complexes potently inhibited translation, as demonstrated by an in-cell translation assay. The effects were seen at 2–15-fold higher concentrations than those required to observe cytotoxicity, suggesting that prevention of protein synthesis may be a primary, but not the exclusive mechanism for the observed cytotoxic activity.

Original languageEnglish
Pages (from-to)790-799
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
StatePublished - Aug 5 2018

Bibliographical note

Funding Information:
This work was supported by the American Cancer Society ( RSG-13-079-01-CDD ). Mass spectrometry analysis was performed at the University of Kentucky Environmental Research Training Laboratory (ERTL).

Publisher Copyright:
© 2018


  • Cancer
  • Coordination chemistry
  • Cytotoxic
  • Ruthenium
  • Translation

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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