Half-Sandwich Ir(III) and Os(II) Complexes of Pyridyl-Mesoionic Carbenes as Potential Anticancer Agents (CROSBI ID 269370)
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Podaci o odgovornosti
Kralj, Juran ; Bolje, Aljoša ; Stupin Polančec, Darija ; Gržan, Tena ; Tupek, Ana ; Steiner, Ivana ; Stojanović, Nikolina ; Hohloch, Stephan ; Urankar, Damijana ; Osmak, Maja ; Sarkar, Biprajit ; Brozovic, Anamaria ; Košmrlj, Janez
engleski
Half-Sandwich Ir(III) and Os(II) Complexes of Pyridyl-Mesoionic Carbenes as Potential Anticancer Agents
A series of cationic chlorido arene-iridium(III) and arene-osmium(II) complexes with bidentate pyridyl functionalized mesoionic carbenes (MIC) of the 1, 2, 3-triazol-5-ylidene type have been prepared. The variations in the ligand structures include the position of the pyridyl substituent relative to the triazolylidene ring (N-wingtip vs. C- wingtip), phenyl versus ethyl substituents, and incorporation of several functional groups at the phenyl substituents. Five complexes have been characterized by X-ray structural analysis. All complexes, including osmium(II) and ruthenium(II) analogues having pyrimidyl in place of pyridyl group, have been studied for their cytotoxic activity on human cervical carcinoma HeLa cell line. Two of the compounds, Ir5 and Ir9, were most cytotoxic with IC50 values of 7.33 μM and 2.01 μM, respectively. Examination of their cytotoxic effect on different cell lines revealed that they preferentially kill cancer over normal cells. The Ir5 and Ir9 compounds arrested cells in G2 and induced dose-dependent increase in SubG0/G1 cell population. The apoptosis, as primary mode of cell death, was confirmed by Annexin V/PI staining, detection of cleaved PARP and caspases 3 and 7 activity upon treatment of HeLa cells with both compounds. The higher toxicity of Ir9 is probably due to its increased accumulation in the cells compared to Ir5. The role of glutathione (GSH) in protection of cells against Ir5 and Ir9 cytotoxicity was confirmed by pre- treatment of cells either with buthionine sulfoximine (inhibitor of GSH synthesis) or N-acetyl-cysteine (precursor in GSH synthesis).
transfer hydrogenation ; biological-activity ; ligands synthesis ; Ir-III ; Ru-II ; Os-II ; Ruthenium(II) ; catalysts ; chloride
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Podaci o izdanju
38 (21)
2019.
4082-4092
objavljeno
0276-7333
1520-6041
10.1021/acs.organomet.9b00327