Dual functions of iridium(III) 2-phenylpyridine complexes: Metastasis inhibition and lysosomal damage.

Author(s) Liu, X.; Chen, S.; Ge, X.; Zhang, Y.; Xie, Y.; Hao, Y.; Wu, D.; Zhao, J.; Yuan, X.A.; Tian, L.; Liu, Z.
Journal J Inorg Biochem
Date Published 2020 Jan 08
Abstract

Six N-phenylcarbazole/triphenylamine-appended half-sandwich iridium(III) 2-phenylpyridine complexes ([(η-Cp*)Ir(C^N)Cl]) were prepared and characterized. Compared with cisplatin, these complexes exhibited potential antitumor activity against A549 and HeLa tumor cells, with IC values (half-maximum inhibitory concentration) that changed from 2.8 ± 0.8 μM to 39.5 ± 2.7 μM, and could block the migration of tumor cells. These complexes also effectively bound to protein (binding constant: ~10 M) and were transported through serum proteins, catalyzed the oxidation of coenzyme nicotinamide-adenine dinucleotide. Additionally, laser confocal microscopy and flow cytometry confirmed that these complexes possessed a non-energy-dependent cellular uptake mechanism, effectively accumulated in lysosomes (Pearson colocalization coefficient: ~0.74), damaged the integrity of acidic lysosomes, led to a change in the mitochondrial membrane potential, disrupted the cell cycle (G/G phase), and eventually induced apoptosis. Above all, these complexes are potential antitumor agents with dual functions: metastasis inhibition and lysosomal damage.

DOI 10.1016/j.jinorgbio.2019.110983
ISSN 1873-3344
Citation Liu X, Chen S, Ge X, Zhang Y, Xie Y, Hao Y, et al. Dual functions of iridium(III) 2-phenylpyridine complexes: Metastasis inhibition and lysosomal damage. J Inorg Biochem. 2020;205:110983.

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