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
