Antibacterial Activity of Co(III) Complexes with Diamine Chelate Ligands against a Broad Spectrum of Bacteria with a DNA Interaction Mechanism.

Katarzyna Turecka,Krzysztof Waleron,Agnieszka Chylewska,Joanna Zakrzewska,Michał Rychłowski

doi:10.3390/pharmaceutics13070946

Abstract

Cobalt coordination complexes are very attractive compounds for their therapeutic uses as antiviral, antibacterial, antifungal, antiparasitic, or antitumor agents. Two Co(III) complexes with diamine chelate ligands ([CoCl2(dap)2]Cl (1) and [CoCl2(en)2]Cl (2)) (where dap = 1,3-diaminopropane, en = ethylenediamine) were synthesized and characterized by elemental analysis, an ATR technique, and a scan method and sequentially tested against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration results revealed that anaerobic and microaerophilic bacteria were found to be the most sensitive; the serial passages assay presented insignificant increases in bacterial resistance to both compounds after 20 passages. The synergy assay showed a significant reduction in the MIC values of nalidixic acid when combined with Compounds (1) or (2). The assessment of cell damage by the complexes was performed using scanning electron microscopy, transmission electron microscopy, and confocal microscopy, which indicated cell membrane permeability, deformation, and altered cell morphology. DNA interaction studies of the Co(III) complexes with plasmid pBR322 using spectrophotometric titration methods revealed that the interaction between Complex (1) or (2) and DNA suggested an electrostatic and intercalative mode of binding, respectively. Furthermore, the DNA cleavage ability of compounds by agarose gel electrophoresis showed nuclease activity for both complexes. The results suggest that the effect of the tested compounds against bacteria can be complex.

Highlights

We hypothesize that the lower antibacterial activity observed for both diamine-chelate Co(III) compounds are due to the active transport out of the bacteria cells
We evaluated the antibacterial activity of Co(III) complexes with a simple bidentate inorganic ligands on a broad spectrum of Gram-positive and Gram-negative bacteria
We hypothesized that the lower activity of compounds against bacteria from the difficulties of overcoming the barrier created by the lipid membranes of bacterial cells, which hinders possible reactions with the target(s) inside the bacterial cell

Summary

Introduction

Increased antimicrobial resistance to the current antibiotics among bacteria is a serious problem globally. To overcome this problem, new and effective antibacterial compounds with low toxicity are needed. A promising group of antimicrobial compounds seem to be metallopharmaceuticals due to their abundance and structural diversity. The most remarkable achievements in the research on this type of compound refer to d-block metal-based drugs. D-block metal ion complexes encounter a large number of biomolecules in biological systems (amino acids, proteins, oligonucleotides, or DNA) and can interact with them

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Conclusion