Half-sandwich Ir(III) and Os(II) complexes of pyridyl-mesoionic carbenes as potential anticancer agents

Kralj, Juran (author), Bolje, Aljoša (author), Stupin Polančec, Darija (author), Steiner, Ivana (author), Gržan, Tena (author), Tupek, Ana (author), Stojanović, Nikolina (author), Hohloch, Stephan (author), Urankar, Damijana (author), Osmak, Maja (author), Sarkar, Biprajit (author), Brozović, Anamaria (author), Košmrlj, Janez (author)

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).

• Language: English
• Keywords: pyridyl-mesoionic carbenes, anticancer agents, iridium, osmium, cells, ligands, precursors, toxicity, transition metals
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2019
• Number of pages: Str. 4082-4092
• Numbering: Vol. 38, iss. 21
• PID: 20.500.12556/RUL-142030
• UDC: 547.79:546.9
• ISSN on article: 0276-7333
• DOI: 10.1021/acs.organomet.9b00327
• COBISS.SI-ID: 1538414787
• Publication date in RUL: 17.10.2022

Record is a part of a journal

• Title: Organometallics
• Shortened title: Organometallics
• Publisher: American Chemical Society
• ISSN: 0276-7333
• COBISS.SI-ID: 16043781

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: piridil-mezoionski karbeni, protirakave substance, iridij, osmij