N-heterocyclic-carbene vs diphosphine auxiliary ligands in thioamidato Cu (I) and Ag(I) complexes towards the development of potent and dual-activity antibacterial and apoptosis-inducing anticancer agents
JOURNAL OF INORGANIC BIOCHEMISTRY(2024)
Abstract
Group 11 metal complexes exhibit promising antibacterial and anticancer properties which can be further enhanced by appropriate ligands. Herein, a series of mononuclear thioamidato Cu(I) and Ag(I) complexes bearing either a diphosphine (P<^>P) or a N -heterocyclic carbene (NHC) auxiliary ligand (L) was synthesized, and the impact of the co-ligand L on the in vitro antibacterial and anticancer properties of their complexes was assessed. All complexes effectively inhibited the growth of various bacterial strains, with the NHC-Cu(I) complex found to be particularly effective against the Gram (+) bacteria (IC50 = 1-4 mu g mL-1). Cytotoxicity studies against various human cancer cells revealed their high anticancer potency and the superior activity of the NHCAg(I) complex (IC50 = 0.95-4.5 mu\M). Flow cytometric analysis on lung and breast cancer cells treated with the NHC-Ag(I) complex suggested an apoptotic cell -death pathway; molecular docking calculations provided mechanistic insights, proving the capacity of the complex to bind on apoptosis-regulating proteins and affect their functionalities.
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Key words
Copper(I) and silver(I) thioamidato complexes,Phosphines,N-heterocyclic carbenes,Antimicrobial activity,Cytotoxicity,Apoptosis
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