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Research Article

Anticancer, antimicrobial and antiparasitical activities of copper(I) complexes based on N-heterocyclic carbene (NHC) ligands bearing aryl substituents

, , , , , , , & show all
Pages 2889-2905 | Received 06 Apr 2020, Accepted 18 Sep 2020, Published online: 08 Nov 2020
 

Abstract

New benzimidazolium salts were synthesized as N-heterocyclic carbene precursors. These NHC precursors were metallated with Cu2O and CuI in acetone and water under reflux to give novel copper(I) complexes. The structures of these benzimidazolium salts and copper(I) complexes were characterized on the basis of elemental analysis, 1H NMR, 13C NMR, IR and LC–MS spectroscopic techniques. The (NHC)Cu(I) complexes 3–4 were tested against MCF7 and MDA-MB-231 cancer cells, Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans microorganisms, Leishmania major promastigotes and amastigotes, Toxoplasma gondii parasites and against Vero cell line in vitro. The synthesized copper NHC carbene complex 4b (1,3-bis(2,3,4,5,6-pentamdthylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-2-yl)copper(I) chloride) was the most active against MCF7 cancer cells (half growth Inhibition Concentrations (IC50) = 0.3 µg mL−1), as well as the most potent antimicrobial against E. coli (inhibition zone (IZ) = 23.3 mm), MRSA (IZ = 25.5 mm) and C. albicans (IZ = 28.5 mm) besides its antileishmanial activities against L. major promastigotes and amastigotes (IC50 < 0.04 µg mL−1). Compound 4c (1,3-bis(4-(tert-butyl)benzyl)-2,3-dihydro-1H-benzo[d]imida-zol-2-yl)copper(II) bromide) is the most potent anticancer against MDA-MB-231 cancer cells IC50 = 0.4 µg mL−1). Compound 4e (5,6-dimethyl-1,3-bis(2,4,6-trimethylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-2-yl)copper(I) chloride) is the best suitable antitoxoplasmal drug candidate due to its SI of 16.5. These candidates need further study to identify mode of action and drug standardization.

Graphical Abstract

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by the Research Supporting Project (RSP2020/75), King Saud University, Riyadh Saudi Arabia.

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