Antimicrobial Activity and DNA/BSA Binding Affinity of Polynuclear Silver(I) Complexes with 1,2-Bis(4-pyridyl)ethane/ethene as Bridging Ligands.

Sonja Ž Đurić,Nevena Lj Stevanović,Miloš I Djuran,Sandra Vojnovic,Jasmina Nikodinovic-Runic,Nada D Savić,Biljana Đ Glišić,Tina P Andrejević

doi:10.1155/2020/3812050

Abstract

1,2-Bis(4-pyridyl)ethane (bpa) and 1,2-bis(4-pyridyl)ethene (bpe) were used for the synthesis of polynuclear silver(I) complexes, {[Ag(bpa)]NO3}n (1), {[Ag(bpa)2]CF3SO3.H2O}n (2) and {[Ag(bpe)]CF3SO3}n (3). In complexes 1–3, the corresponding nitrogen-containing heterocycle acts as a bridging ligand between two Ag(I) ions. In vitro antimicrobial activity of these complexes, along with the ligands used for their synthesis, was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and fungi. The silver(I) complexes 1–3 showed selectivity towards Candida spp. and Gram-negative Escherichia coli in comparison to the other investigated bacterial strains, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MICs) between 2.5 and 25 μg/mL and the growth of E. coli, with MIC value being 12.5 μg/mL. Importantly, complex 2 significantly reduced C. albicans filamentation, an essential process for its pathogenesis. Antiproliferative effect on the normal human lung fibroblast cell line MRC-5 was also evaluated with the aim of determining the therapeutic potential of the complexes 1–3. The interactions of these complexes with calf thymus DNA (ctDNA) and bovine serum albumin (BSA) were studied to evaluate their binding activities towards these biomolecules for possible insights on their mode of action.

Highlights

IntroductionSilver(I) complexes showed effective and wide-spectrum antimicrobial activity, including the strains which are resistant to the currently used antimicrobials, while their toxicity to the normal human cells was not pronounced [6]
In vitro antimicrobial activity of these complexes, along with the ligands used for their synthesis, was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and fungi. e silver(I) complexes 1–3 showed selectivity towards Candida spp. and Gram-negative Escherichia coli in comparison to the other investigated bacterial strains, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MICs) between 2.5 and 25 μg/mL and the growth of E. coli, with MIC value being 12.5 μg/mL
Measurements. e elemental analyses of the synthesized silver(I) complexes for carbon, hydrogen, and nitrogen were performed by the Microanalytical Laboratory, Faculty of Chemistry, University of Belgrade. e 1H and 13C NMR spectra of the N-heterocyclic ligands and the silver(I) complexes were recorded at room temperature on a Varian Gemini 2000 spectrometer (1H at 200 MHz, 13C at 50 MHz). 5.0 mg of each compound was dissolved in 0.6 mL of DMSOd6 and transferred into a 5 mm NMR tube

Summary

Introduction

Silver(I) complexes showed effective and wide-spectrum antimicrobial activity, including the strains which are resistant to the currently used antimicrobials, while their toxicity to the normal human cells was not pronounced [6]. Us, silver(I) complexes with various aromatic nitrogen-donor ligands have shown remarkable and broad-spectrum antimicrobial activity against a panel of bacterial and fungal strains as a consequence of a relatively weak Ag–N bond which can be cleaved in the reactions with biological target molecules [13–21]. As a continuation of our efforts in the synthesis of silver(I) complexes as potential antimicrobial agents, in the present study, we used two aromatic nitrogen-containing heterocycles (N-heterocycles) in which two pyridine rings are linked by–CH2–CH2– and–CH═CH–groups, 1,2-bis(4pyridyl)ethane (bpa) and 1,2-bis(4-pyridyl)ethene (bpe), respectively. E complexes were evaluated for their in vitro antimicrobial activity and the effect on the viability of a human normal fibroblast cell line (MRC-5). In order to gain an insight into the reactivity of complexes 1–3 with potential biological targets, their interactions with the calf thymus DNA (ctDNA) and bovine serum albumin (BSA) were examined

Methods

Results

Conclusion