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

作者: Dmytro Havrylyuk , Brock S. Howerton , Leona Nease , Sean Parkin , David K. Heidary

DOI: 10.1016/J.EJMECH.2018.04.044

关键词: Coordination complexStereochemistryClioquinolCytotoxicityChemistryRutheniumBiological activityCytotoxic T cellMechanism of actionHydroxyquinolines

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

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