Antimicrobial and Anticancer Application of Silver(I) Dipeptide Complexes.

Gabriela Kuzderová,Danica Sabolová,Petra Olejníková,Mária Vilková,Ivana Bačová,Simona Sovová,Martin Kello,Michaela Rendošová,Zuzana Vargová,Simonida Stokič,Róbert Gyepes

doi:10.3390/molecules26216335

Abstract

Three silver(I) dipeptide complexes [Ag(GlyGly)]n(NO3)n (AgGlyGly), [Ag2(GlyAla)(NO3)2]n (AgGlyAla) and [Ag2(HGlyAsp)(NO3)]n (AgGlyAsp) were prepared, investigated and characterized by vibrational spectroscopy (mid-IR), elemental and thermogravimetric analysis and mass spectrometry. For AgGlyGly, X-ray crystallography was also performed. Their stability in biological testing media was verified by time-dependent NMR measurements. Their in vitro antimicrobial activity was evaluated against selected pathogenic microorganisms. Moreover, the influence of silver(I) dipeptide complexes on microbial film formation was described. Further, the cytotoxicity of the complexes against selected cancer cells (BLM, MDA-MB-231, HeLa, HCT116, MCF-7 and Jurkat) and fibroblasts (BJ-5ta) using a colorimetric MTS assay was tested, and the selectivity index (SI) was identified. The mechanism of action of Ag(I) dipeptide complexes was elucidated and discussed by the study in terms of their binding affinity toward the CT DNA, the ability to cleave the DNA and the ability to influence numbers of cells within each cell cycle phase. The new silver(I) dipeptide complexes are able to bind into DNA by noncovalent interaction, and the topoisomerase I inhibition study showed that the studied complexes inhibit its activity at a concentration of 15 μM.

Highlights

For the second year in a row, humanity has been facing the pandemic caused by COVID-19 disease
Based on our above-mentioned experience, in the step we focused on the preparation and characterization of silver(I) complexes with selected dipeptides in order to study their antimicrobial and anticancer activity, their toxicity, their selectivity as well as their possible mechanism of action at the nuclear level (DNA interactions, DNA cleavage, cell cycle arrest)
The compounds AgGlyGly, AgGlyAla and AgGlyAsp were isolated from an aqueous solution of AgNO3 and appropriate dipeptide at a 1:1 species:molar ratio of AgNO3 : HGlyGly/HGlyAla/H2 GlyAsp

Summary

Introduction

For the second year in a row, humanity has been facing the pandemic caused by COVID-19 disease. The fact that this pandemic causes a huge loss of life is a direct impact of the activity of this strain of viruses. It is natural that after two years, patients with various advanced infectious and cancerous diseases are beginning to appear in hospitals and outpatient clinics. This fact leads to the requirement for scientists to work intensively on the development of effective and selective antimicrobials and anticancer drugs. It is important to know what natural mechanisms the immune system in our organisms uses and to find approaches to help support this system

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