Structural Characterization, Antimicrobial Activity and BSA/DNA Binding Affinity of New Silver(I) Complexes with Thianthrene and 1,8-Naphthyridine.

Biljana Đ Glišić,Jasmina Nikodinovic-Runic,Tina P Andrejević,Ivana Aleksic,Sanja Skaro Bogojevic,Iztok Turel,Franc Perdih,Miloš I Djuran,Darko P Ašanin,Dusan Milivojevic

doi:10.3390/molecules26071871

Abstract

Three new silver(I) complexes [Ag(NO3)(tia)(H2O)]n (Ag1), [Ag(CF3SO3)(1,8-naph)]n (Ag2) and [Ag2(1,8-naph)2(H2O)1.2](PF6)2 (Ag3), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three Candida species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and the investigated Candida species with minimal inhibitory concentration (MIC) values in the range 1.56–7.81 μg/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model Caenorhabditis elegans. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of Ag1–3 to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids.

Highlights

Infections caused by bacteria and fungi threaten human health on a daily basis because many microbes have developed resistance to the commercial antimicrobial agents over time [1]
The problems related to the microbial infections and resistance occurrence demand urgent and effective solution, which is based on the development of novel antimicrobial agents
The antiproliferative effect of these complexes was considerably higher but comparable to the observed minimal inhibitory concentration (MIC) values (Table 4). This may limit the antimicrobial application of these complexes, but it is worth mentioning that silver(I) complexes with different classes of ligands have been studied for their antitumor potential and some of them showed antiproliferative activities higher than cisplatin [51]. These results are in line with our previous work in which we showed that the silver(I) complexes with a 1,5-naphthyridine ligand, which is a structural isomer of 1,8-naph, have remarkable activity against a range of Candida species, while for the tested bacterial species, MIC values obtained in this study are 2–3 times lower than in our previously published work (Table 4) [31]

Summary

Introduction

Infections caused by bacteria and fungi threaten human health on a daily basis because many microbes have developed resistance to the commercial antimicrobial agents over time [1]. The mechanism of antimicrobial activity of the silver(I) complexes is explained by their slow release of Ag(I) ions [10,11] These ions can interact with the bacterial cell surfaces, enabling their penetration into the cell. Ag(I) ions could interact with the biomolecules in its interiors, such as DNA and proteins They can cause the production of reactive oxygen species (ROS), leading to bacterial cell death [10,11]. Due to this multi-targeting mechanism, the silver(I) complexes act as antimicrobial agents, which might overcome the problem of bacterial resistance [12]

Methods

Results

Conclusion