Relation of Metal-Binding Property and Selective Toxicity of 8-Hydroxyquinoline Derived Mannich Bases Targeting Multidrug Resistant Cancer Cells

Resistance to chemotherapeutic agents is a major obstacle in cancer treatment. A recently proposed strategy target the collateral sensitivity of multidrug resistant (MDR) cancer. Paradoxically, toxicity certain metal chelating increased, rather than decreased, by function P-glycoprotein (Pgp), which known confer resistance effluxing compounds from cells. We have characterized and compared solution’s chemical properties including ligand protonation binding set structurally related 8-hydroxyquinoline derived Mannich bases. Here we characterize impact solution stability redox activity their iron(III) copper(II) complexes on MDR-selective toxicity. Our results show that anticancer studied bases associated with iron deprivation MDR cells preferential formation redox-active complexes, undergo intracellular redox-cycling induce oxidative stress.