Ligand-centred redox activation of inert organoiridium anticancer catalysts.

ABSTRACT: Organometallic complexes with novel activation mechanisms are attractive anticancer drug candidates. Here, we show that half-sandwich iodido cyclopentadienyl iridium(iii) azopyridine complexes exhibit potent antiproliferative activity towards cancer cells, in most cases more potent than cisplatin. Despite their inertness towards aquation, these iodido complexes can undergo redox activation by attack of the abundant intracellular tripeptide glutathione (GSH) on the chelated azopyridine ligand to generate paramagnetic intermediates, and hydroxyl radicals, together with thiolate-bridged dinuclear iridium complexes, and liberate reduced hydrazopyridine ligand. DFT calculations provided insight into the mechanism of this activation. GS^- attack on the azo bond facilitates the substitu

SUBMITTER: Zhang WY 

PROVIDER: S-EPMC8159363 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature