Evaluation of Ruthenium(II) N-Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase

Abstract

A series of ruthenium(II) complexes with N-heterocyclic carbene (NHC) ligands of the general type (arene)(NHC)Ru(II)X2 (where X = halide) was prepared, characterized, and evaluated as antibacterial agents in comparison to the respective metal free benzimidazolium cations. The ruthenium(II) NHC complexes generally triggered stronger bacterial growth inhibition than the metal free benzimidazolium cations. The effects were much stronger against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) than against Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa), and all complexes were inactive against the fungus Candida albicans. Moderate inhibition of bacterial thioredoxin reductase was confirmed for selected complexes, indicating that inhibition of this enzyme might be a contributing factor to the antibacterial effects.

Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones

“…Complexes 1a , 1c and 2d showed no antibacterial effect; however, complexes 1d and 2c , as can be observed in Table 1 , displayed the ‘classical’ antibacterial effect of gold derivatives since they were able to inhibit the growth of all Gram-positive bacterial strains, but were inactive against Gram-negative strains. These results suggest that both complexes might inhibit bacterial thioredoxin reductase (TrxR), the most common target for gold compounds, as previously reported for auranofin [ 44 , 55 , 56 ], as well as other gold complexes and ruthenium derivatives with N-heterocyclic carbene ligands [ 57 , 58 , 59 ]. Contrarily, complexes 1b and 2b were found able to interfere with the development of both Gram positive and Gram negative strains, the effect of the complex coordinated with the carbene IMe ([Au(L2b)(IMe)] ( 1b )) being greater than that detected for its counterpart with IPr ([Au(L2b)(IPr)] ( 2b )).…”

Metallodrug Profiling against SARS‐CoV‐2 Target Proteins Identifies Highly Potent Inhibitors of the S/ACE2 interaction and the Papain‐like Protease PLpro

“…Some tested compounds are commercially available and they were purchased from Sigma Aldrich (sodium aurothiomalate hydrate, gold(III) chloride hydrate, chloro(triethylphosphine)gold(I), chloro(triphenylphosphine)gold(I), thiomersal), Acros Organics (silver sulfadiazine, titanocene dichoride, cisplatin, disulfiram), Adipogen‐Biomol (chloroquine diphosphate) and Enzo Life Sciences (auranofin). The following complexes were prepared as previously described in the literature: Au‐7 [51] , Au‐8 [52] , Au‐9 , Au‐11 [53] , Au10 [54] , Au‐12 , Au‐13 [55] , Au‐15 [52] , Au‐20 , Au‐25 , Au‐26 [56] , Au‐27 [57] , Au‐31 – Au‐32 [55] , Au‐33 , Au‐34 [58] , Ru‐1 , Ru‐4 – Ru‐8 , [59] , Ru‐10 [60] , Ru‐11 [61] , Ru‐12 [62] , Ru‐13 [63] , Ru‐14 , Ru‐15 , Ru‐16 [64] , Mn‐1 , Mn‐2 [65] , Re‐1 [66] , Re‐2 [67] , Pt‐2 [68] , Pt‐3 , Pt‐4 , Pd‐1 , Pd‐2 [69] , Fe‐1 , Fe‐2 , Fe‐3 , Fe‐4 [70] , Fe‐5 [71] , Fe‐6 [72] , Fe‐7 , Fe‐8 [73] Fe‐9 [74] , Fe‐10 [75] , Fe‐11 [76] , Fe‐13 [77] , POM‐1 , POM‐2 [27] , POM‐3 [28] , POM‐4 [29] , POM‐5 [30] , POM‐6 , POM7 [31] …”

Ruthenium Complex HB324 Induces Apoptosis via Mitochondrial Pathway with an Upregulation of Harakiri and Overcomes Cisplatin Resistance in Neuroblastoma Cells In Vitro

“…We and others have recently reported on ruthenium(+2/+3) complexes with N-heterocyclic carbene (NHC) ligands [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ] and their potential as novel anticancer drugs. For complexes of the type [(p-cymene)(NHC)RuCl2], we observed strong cytotoxic effects when the NHC ligand contained benzyl side chains on the nitrogen atoms of the NHC ligand that facilitated an efficient cellular uptake [ 23 ].…”

“…Interestingly, HB320 triggered toxicity in zebrafish embryos at concentrations higher than the half maximal inhibitory concentration (IC 50 ) values for anticancer cell toxicity, indicating a certain degree of selectivity. Complex HB324 was recently described with a series of antibacterial ruthenium complexes, where it triggered moderate activity against some gram-positive pathogenic bacteria [ 19 ].…”