Silver (I) N-Heterocyclic Carbene Complexes: A Winning and Broad Spectrum of Antimicrobial Properties.

Filippo Prencipe,Luisa Ronga,Mario Varcamonti,Michele Saviano,Filomena Rossi,Anna Zanfardino,Gennaro Piccialli,Diego Tesauro,Michela Di Napoli,Giuseppe Felice Mangiatordi,Stefano D’Errico

doi:10.3390/ijms22052497

Abstract

The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics. N-Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC-carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC-Ag neutral and bis NHC-Ag cationic complexes. Their inhibitor effect on bacterial strains Gram-negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms.

Highlights

The evolution of antimicrobial resistance to most drugs pushes researchers to develop novel, more potent, and multimodal alternatives with least antibiotic effects on the human body
The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics
Pyrazole N-Heterocyclic Carbenes (NHCs) silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties

Summary

Introduction

The evolution of antimicrobial resistance to most drugs pushes researchers to develop novel, more potent, and multimodal alternatives with least antibiotic effects on the human body In this scenario, future applications can come from metal based compounds. The observed resistance mechanisms led to the renaissance of silver-based antimicrobial research in the ‘60s [2] and silver based compounds in XXI century can play a relevant role in fights against infections. The success of this metal lies in the effectiveness at low concentrations and in the low toxicity. The nature of the atom coordinated to the metal center and its bonding properties play a decisive role, rather than the chirality of the ligands, solubility, charge, or degree of polymerization of the silver complexes

Results

Discussion

Conclusion