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 complex 、 Stereochemistry 、 Clioquinol 、 Cytotoxicity 、 Chemistry 、 Ruthenium 、 Biological activity 、 Cytotoxic T cell 、 Mechanism of action 、 Hydroxyquinolines
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.