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Structure-activity relationships for highly potent half-sandwich organoiridium(III) anticancer complexes with C^N-chelated ligands.
Journal of Inorganic Biochemistry 2018 November 11
We herein report the synthesis, characterization, catalytic ability in converting coenzyme NADH to NAD+ and anticancer activity of half-sandwich iridium(III) complexes, [(η5 -Cpxbiph )Ir(C^N)Cl]PF6 - , where Cpxbiph = tetramethyl(biphenyl)cyclopentadienyl, C^N = varying imine-N-heterocyclic carbene ligands. The molecular structure of [(η5 -Cpxbiph )Ir(L6)Cl]PF6 (complex Ir6), exhibiting the familiar "piano-stool" geometry, has been authenticated by X-ray crystallography. The anticancer activities of these complexes can be governed via substituent effects of three tunable domains and the ligand substituted variants offer an effective chelate ligand set that distinguishes anticancer activity and catalytic ability. Notably, complex Ir6 displays the greatest cytotoxic activities (IC50 = 0.85 μM), whose anticancer activity is more approximately 25-fold higher than that of cisplatin. The initial cell death mechanistic insight displays that this group of iridium(III) complexes exerts anticancer effects via cell cycle arrest, apoptosis induction and loss of the mitochondrial membrane potential. In addition, the confocal microscopy imaging shows that the complex Ir6 can damage lysosome. Overall, preliminary structure-activity relationships study and understanding of the cell death mechanism perhaps provide a rational strategy for enhancing anticancer activity of this family of complexes.
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