Chemical Characterization and Biological Evaluation of New Cobalt(II) Complexes with Bioactive Ligands, 2-Picolinehydroxamic Acid and Reduced Schiff Base N-(2-Hydroxybenzyl)alanine, in Terms of DNA Binding and Antimicrobial Activity.

Magdalena Woźniczka,Weronika Gonciarz,Marta Lichawska,Manas Sutradhar,Magdalena Chmiela,Marek Pająk

doi:10.3390/ph14121254

Magdalena Woźniczka, Weronika Gonciarz + Show 4 more

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https://doi.org/10.3390/ph14121254

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Abstract

Five new heteroligand cobalt(II) complexes with 2-picolinehydroxamic acid and reduced Schiff base, N-(2-hydroxybenzyl)alanine, were formed in an aqueous solution over a wide pH range. The coordination properties of ligands towards the metal ion were determined using a pH-metric method, and then the speciation model was confirmed by UV–Vis studies. A stacking interaction between the Schiff base phenol ring and the 2-picolinehydroxamic acid pyridine ring was found to improve the stability of the heteroligand species, indicating more effective coordination in mixed-ligand complexes than in their respective binary systems. The antimicrobial properties of heteroligand complexes were determined against Gram-negative and Gram-positive bacteria, as well as fungal strains. The formulation demonstrated the highest bacteriostatic and bactericidal activity (3.65 mM) against two strains of Gram-negative Helicobacter pylori bacteria and towards Candida albicans and Candida glabrata; this is important due to the potential co-existence of these microorganisms in the gastric milieu and their role in the development of gastritis. The binary complexes in the cobalt(II)—2-picolinehydroxamic acid system and 2-picolinehydroxamic acid were not cytotoxic against L929 mouse fibroblasts, neither freshly prepared solutions or after two weeks’ storage. By comparison, the heteroligand complexes within the range 0.91–3.65 mM diminished the metabolic activity of L929 cells, which was correlated with increased damage to cell nuclei. The concentration of the heteroligand species increased over time; therefore, the complexes stored for two weeks exhibited stronger anticellular toxicity than the freshly prepared samples. The complexes formed in an aqueous solution under physiological pH effectively bound to calf thymus DNA in an intercalative manner. This DNA-binding ability may underpin the antimicrobial/antifungal activity of the heteroligand complexes and their ability to downregulate the growth of eukaryotic cells.

Highlights

IntroductionThe development of resistance to antibiotics and other agents, such as anticancer, antifungal and antiviral drugs, is a major problem in clinical practice because it reduces the effectiveness of treatment, causing increased morbidity and mortality [1,2,3,4,5,6]
Heteroligand structures play an important role in biological processes [8,9,10,11], and model systems containing aromatic amines as the primary ligand and amino acid derivatives as the secondary ligand could be used to better understand the transport of metal ions and active substances through membranes and biochemical reactions catalyzed by metalloenzymes [12]
Our potentiometry results confirmed the presence of five heteroligand complexes in the equilibrium mixture formed by 2-picolinehydroxamic acid (PicHA) and N-(2hydroxybenzyl)alanine (AlaSal) with Co(II)

Summary

Introduction

The development of resistance to antibiotics and other agents, such as anticancer, antifungal and antiviral drugs, is a major problem in clinical practice because it reduces the effectiveness of treatment, causing increased morbidity and mortality [1,2,3,4,5,6]. When looking for new drugs, a range of pharmacologically promising compounds should be evaluated, and this evaluation should include their chemical and biological properties. Heteroligand structures play an important role in biological processes [8,9,10,11], and model systems containing aromatic amines as the primary ligand and amino acid derivatives as the secondary ligand could be used to better understand the transport of metal ions and active substances through membranes and biochemical reactions catalyzed by metalloenzymes [12]. To confirm the structure and stability of a particular heteroligand species, it is necessary to determine the interaction between two ligands bound to the same metal ion

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