Triazolyl‐Functionalized N ‐Heterocyclic Carbene Half‐Sandwich Compounds: Coordination Mode, Reactivity and in vitro Anticancer Activity
| Autor: | Christian G. Hartinger, Sanam Movassaghi, Kelvin K. H. Tong, James H. Lovett, Suresh K. Bhargava, Katja Hummitzsch, Hugh H. Harris, Stephen M. F. Jamieson, Muhammad Hanif, Tilo Söhnel, Matthew P. Sullivan |
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| Rok vydání: | 2021 |
| Předmět: |
Denticity
Cell Survival Stereochemistry Antineoplastic Agents Biochemistry Metal Structure-Activity Relationship chemistry.chemical_compound Coordination Complexes Heterocyclic Compounds Cell Line Tumor Drug Discovery Humans Moiety Reactivity (chemistry) General Pharmacology Toxicology and Pharmaceutics Density Functional Theory Cell Proliferation Pharmacology Aqueous solution Dose-Response Relationship Drug Molecular Structure Ligand Organic Chemistry Triazoles chemistry visual_art Lipophilicity visual_art.visual_art_medium Molecular Medicine Drug Screening Assays Antitumor Methane Carbene |
| Zdroj: | ChemMedChem. 16:3017-3026 |
| ISSN: | 1860-7187 1860-7179 |
| DOI: | 10.1002/cmdc.202100311 |
| Popis: | We report investigations on the anticancer activity of organometallic [MII/III (η6 -p-cymene/η5 -pentamethylcyclopentadienyl)] (M=Ru, Os, Rh, and Ir) complexes of N-heterocyclic carbenes (NHCs) substituted with a triazolyl moiety. Depending on the precursors, the NHC ligands displayed either mono- or bidentate coordination via the NHC carbon atom or as N,C-donors. The metal complexes were investigated for their stability in aqueous solution, with the interpretation supported by density functional theory calculations, and reactivity to biomolecules. In vitro cytotoxicity studies suggested that the nature of both the metal center and the lipophilicity of the ligand determine the biological properties of this class of compounds. The IrIII complex 5 d bearing a benzimidazole-derived ligand was the most cytotoxic with an IC50 value of 10 μM against NCI-H460 non-small cell lung carcinoma cells. Cell uptake and distribution studies using X-ray fluorescence microscopy revealed localization of 5 d in the cytoplasm of cancer cells. |
| Databáze: | OpenAIRE |
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