20.500.12556/RUL-142030 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 a pyrimidyl in place of the pyridyl group, have been studied for their cytotoxic activity on a human cervical carcinoma HeLa cell line. Two of the compounds, Ir$^5$ and Ir$^9$, were the most cytotoxic with IC$_{50}$ 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 Ir$^5$ and Ir$^9$ compounds arrested cells in G2 and induced a dose-dependent increase in SubG0/G1 cell population. Apoptosis, as the 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 Ir$^9$ is probably due to its increased accumulation in the cells compared to Ir$^5$ . The role of glutathione (GSH) in the protection of cells against Ir$^5$ and Ir$^9$ cytotoxicity was confirmed by pretreatment of cells either with buthionine sulfoximine (inhibitor of GSH synthesis) or N-acetyl-cysteine (precursor in GSH synthesis). pyridyl-mesoionic carbenes anticancer agents iridium osmium cells ligands precursors toxicity transition metals piridil-mezoionski karbeni protirakave substance iridij osmij true false true Angleški jezik Slovenski jezik Članek v reviji 2022-10-17 10:33:46 2022-10-17 10:33:47 2025-04-25 11:41:42 0000-00-00 00:00:00 2019 0 0 Str. 4082-4092 iss. 21 Vol. 38 11 Nov. 2019 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 547.79:546.9 0276-7333 10.1021/acs.organomet.9b00327 1538414787 kralj-et-al-2019-half-sandwich-ir(iii)-and-os(ii)-complexes-of-pyridyl-mesoionic-carbenes-as-potential-anticancer-agents.pdf kralj-et-al-2019-half-sandwich-ir(iii)-and-os(ii)-complexes-of-pyridyl-mesoionic-carbenes-as-potential-anticancer-agents.pdf 1 F92836080D40B23B11871E389578DE2E ca7a094bcee4ed113aa1c6c11c4a7dab82f3ca40c655feb37f92ed33c80b06f2 167fc199-1acd-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=208541 https://pubs.acs.org/doi/10.1021/acs.organomet.9b00327 1 5eb91af2-4df6-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=163278 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0