Triazolyl-Functionalized N-Heterocyclic Carbene Half-Sandwich Compounds: Coordination Mode, Reactivity and in vitro Anticancer Activity.

Autor: Tong KKH; School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.; Maurice Wilkins Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand., Hanif M; School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.; Maurice Wilkins Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand., Movassaghi S; School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand., Sullivan MP; School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.; Maurice Wilkins Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.; School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand., Lovett JH; Department of Chemistry, The University of Adelaide, Adelaide, SA 5005, Australia., Hummitzsch K; Discipline of Obstetrics and Gynecology, The University of Adelaide, Robinson Research Institute, Adelaide, SA 5005, Australia., Söhnel T; School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand., Jamieson SMF; Maurice Wilkins Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.; Auckland Cancer Society Research Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand., Bhargava SK; Centre for Advanced Materials and Industrial Chemistry, School of Science, RMIT University, Melbourne, Australia., Harris HH; Department of Chemistry, The University of Adelaide, Adelaide, SA 5005, Australia., Hartinger CG; School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.; Maurice Wilkins Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2021 Oct 06; Vol. 16 (19), pp. 3017-3026. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1002/cmdc.202100311
Abstrakt: We report investigations on the anticancer activity of organometallic [M II/III (η 6 -p-cymene/η 5 -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 Ir III complex 5 d bearing a benzimidazole-derived ligand was the most cytotoxic with an IC 50 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.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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