Synthesis, characterization and molecular docking studies of iridium(III) complex with substituted morpholine for glioblastoma cells.

A new iridium(III) complex containing 2-(1H-benzimidazol-2-yl) quinoline functionalized with morpholine moiety (Ir-Morph) was synthesized and characterized by FT-IR, NMR, HRMS mass spectrometry, UV-Vis absorption-emission spectroscopy and cyclic voltammetry. The anticancer activity of iridium complex has been evaluated on U87 and LN18 glioblastoma cell lines. To further assess the impact of Ir-Morph on glioblastoma cell viability at the cellular level, U87 and LN18 cells were stained with DiOC₆ and fluorescence intensity was quantified under different Ir-Morph treatments. Molecular docking studies were conducted to explore the predicted binding modes and relative docking scores of Ir-Morph with selected target proteins associated with treatment resistance, cell proliferation, and apoptotic escape in glioblastoma. Immunoblotting was subsequently performed to evaluate Ir-Morph-associated changes in the expression or phosphorylation of selected proteins. The results of our study revealed that Ir-Morph decreased the cell viablity of both glioblastoma cell lines by causing cytotoxic effects. Ir-Morph treatments also reduced mitochondrial membrane potential suggesting that apoptotic cell death was activated. This fact was supported by the increased PARP cleavage in U87 and LN18 cells. Our findings showed that both total and phosphorylated Akt level increased following even high concentration of Ir-Morph exposure in both cell lines, suggesting that GBM cells keep Akt signaling. We also detected crucial proteins in drug ressitance in glioblastoma were upregulated in U87 but remained same in LN18 cells, suggesting that increased resistance response is not essential to prevent Ir-Morph -induced apoptotic cell death.