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Issue 38, 2016
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Cyclometallated iridium complexes inducing paraptotic cell death like natural products: synthesis, structure and mechanistic aspects

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Abstract

Six mononuclear Ir complexes (1–6) using polypyridyl-pyrazine based ligands (L1 and L2) and {[cp*IrCl(μ-Cl)]2 and [(ppy)2Ir(μ-Cl)]2} precursors have been synthesised and characterised. Complexes 1–5 have shown potent anticancer activity against various human cancer cell lines (MCF-7, LNCap, Ishikawa, DU145, PC3 and SKOV3) while complex 6 is found to be inactive. Flow cytometry studies have established that cellular accumulation of the complexes lies in the order 2 > 1 > 5 > 4 > 3 > 6 which is in accordance with their observed cytotoxicity. No changes in the expression of the proteins like PARP, caspase 9 and beclin-1, Atg12 discard apoptosis and autophagy, respectively. Overexpression of CHOP, activation of MAPKs (P38, JNK, and ERK) and massive cytoplasmic vacuolisation collectively suggest a paraptotic mode of cell death induced by proteasomal dysfunction as well as endoplasmic reticulum and mitochondrial stress. An intimate relationship between p53, ROS production and extent of cell death has also been established using p53 wild, null and mutant type cancer cells.

Graphical abstract: Cyclometallated iridium complexes inducing paraptotic cell death like natural products: synthesis, structure and mechanistic aspects

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Publication details

The article was received on 08 Mar 2016, accepted on 16 Aug 2016 and first published on 17 Aug 2016


Article type: Paper
DOI: 10.1039/C6DT00929H
Citation: Dalton Trans., 2016,45, 15122-15136

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    Cyclometallated iridium complexes inducing paraptotic cell death like natural products: synthesis, structure and mechanistic aspects

    S. K. Tripathy, U. De, N. Dehury, P. Laha, M. K. Panda, H. S. Kim and S. Patra, Dalton Trans., 2016, 45, 15122
    DOI: 10.1039/C6DT00929H

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