2018 journal article
Structure-activity relationships of anticancer ruthenium(II) complexes with substituted hydroxyquinolines
European Journal of Medicinal Chemistry, 156, 790–799.
Contributors: D. Havrylyuk *, B. Howerton*, L. Nease*, S. Parkin *, D. Heidary * & E. Glazer *
MeSH headings : Antineoplastic Agents / chemistry; Antineoplastic Agents / pharmacology; Cell Line, Tumor; Coordination Complexes / chemistry; Coordination Complexes / pharmacology; Humans; Hydroxyquinolines / chemistry; Hydroxyquinolines / pharmacology; Ligands; Models, Molecular; Neoplasms / drug therapy; Neoplasms / genetics; Protein Biosynthesis / drug effects; Ruthenium / chemistry; Ruthenium / pharmacology; Structure-Activity Relationship; Transcription, Genetic / drug effects
TL;DR:
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.
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Source: ORCID
Added: November 30, 2023
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.