Gold(I) and Gold(III) N‐Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase

Abstract

A series of (NHC)Au(I)Cl monocarbene complexes and their gold(III) analogues (NHC)Au(III)Cl3 were prepared and investigated as antibacterial agents and inhibitors of bacterial TrxR. The complexes showed stronger antibacterial effects against the Gram‐positive MRSA and E. faecium strains than against several Gram‐negative bacteria. All complexes were efficient inhibitors of bacterial thioredoxin reductase, indicating that inhibition of this enzyme might be involved in their mechanism of action. The efficacy of gold(I) and gold(III) analogues was comparable in most of the assays. The cytotoxicity of the gold NHC compounds against cancer and human cells was overall weaker than the activity against the Gram‐positive bacteria, suggesting that their optimization as antibacterials warrants further investigation.

A C∧S-Cyclometallated Gold(III) Complex as a Novel Antibacterial Candidate Against Drug-Resistant Bacteria

“…These results are especially significant considering that the higher efficacy of 2 compared with CIP and TOB is also observed in the pan-resistant strain AbCr17. This preference for Gram-positive pathogens and stronger activity toward A. baumannii has been recently reported for gold NHC complexes and also for the reference gold(I) complex drug auranofin, together with a consistently higher antibacterial activity noted for gold(III) NHC complexes, compared with gold(I) analogs (Büssing et al, 2021).…”

“…In recent years, medicinal applications of gold(I)-NHC complexes focused mostly on their anticancer activity (Samanta et al, 2015;Mora et al, 2019;Patil et al, 2020;Behera et al, 2021;Guarra et al, 2021). In contrast, notably fewer contributions describing significant antimicrobial activities have been reported (Roymahapatra et al, 2012;Samanta et al, 2013;Büssing et al, 2021;Hussaini et al, 2021;Jakob et al, 2021).…”

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] …”

Gold-Derived Molecules as New Antimicrobial Agents

“…Au(III) NHC complexes 25 – 27 showed higher antibacterial activity against the Gram-positive MRSA and E. faecium than against the Gram-negative strains ( A. baumannii , E. coli , Klebsiella pneumoniae , and P. aeruginosa ), as previously reported for the related Au(I) NHC complexes. All target complexes were efficient inhibitors of bacterial TrxR, suggesting that inhibition of this enzyme might be involved in the mechanism of antibacterial activity ( Büssing et al, 2021 ).…”