The structural features of copper(II), nickel(II), cobalt(II) and zinc(II) complexes with the antimicrobial drugs quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) as ligands are discussed. The binding properties of these complexes to biomolecules (calf-thymus DNA, bovine or human serum albumin) are presented and evaluated. The biological activity (antimicrobial, antioxidant and antiproliferative) of selected complexes is investigated. Further perspectives concerning the synthesis and the biological activity of novel complexes with quinolones or NSAIDs attractive to synthetic chemists, biochemists and/or biologists are presented.

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Quinolones and non-steroidal anti-inflammatory drugs interacting with copper(II), nickel(II), cobalt(II) and zinc(II): structural features, biological evaluation and perspectives

Background: As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Objective: Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Conclusion: Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic...

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Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites.

Nickel–quinolones interaction: Part 5—Biological evaluation of nickel(II) complexes with first-, second- and third-generation quinolones

ATP-binding cassette (ABC) transporters are essential proteins that are found across all kingdoms of life. ABC transporters harness the energy of ATP hydrolysis to drive the import of nutrients inside bacterial cells or the export of toxic compounds or essential lipids across bacteria and eukaryotic membranes. Typically, ABC transporters consist of transmembrane domains (TMDs) and nucleotide-binding domains (NBDs) to bind their substrate and ATP, respectively. The TMDs dictate what ligands can be recognised, whereas the NBDs are the power engine of the ABC transporter, carrying out ATP binding and hydrolysis. It has been proposed that they utilise the alternating access mechanism, inward- to outward-facing conformation, to transport their substrates. Here, we will review the recent progress on the structure determination of eukaryotic and bacterial ABC transporters as well as the novel mechanisms that have also been proposed, that fall out of the alternating access mechanism model.

Learning the ABCs one at a time: structure and mechanism of ABC transporters.

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

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Structures and properties of naturally occurring polyether antibiotics.

Synthesis, structure and antimicrobial activity of manganese(II) and cobalt(II) complexes of the polyether ionophore antibiotic Sodium Monensin A.

Crystal structure and properties of the copper(II) complex of sodium monensin A.

The complexation of carboxylic acid Monensin A (MonH, 1a) with CoCl2.6H2O and MnCl2.4H2O leads to the formation of mononuclear complexes [Co(Mon)2(H2O)2], 2a and [Mn(Mon)2(H2O)2], 2b, respectively. The unique crystal structures of 2a and 2b were determined by X-ray crystallography. The complexes crystallize in the monoclinic space group P21 with an octahedrally coordinated transition metal center forming the crystallographically centrosymmetric chromophore CoO6 or MnO6, respectively. Two molecules of Monensin A act bidentately through their carboxylate moiety and a hydroxyl group, and two water molecules are additionally transcoordinated. Although the transition metal ions are not bound into the cavity of the ligand, the unusual bidentate coordination mode of the ionophore induces its “pseudo-cyclization” forming 22-membered cycles further stabilized by a number of H-bonds. The complexes are the first example of divalent metal complexes of the monovalent polyether ionophore. The parallel study on the complexation ability of the potassium complex of Monensin A (MonK, 1b) towards Co(II) and Mn(II) showed the formation of the isostructural complexes 2a and 2b accompanied by loss of the potassium ion due to the new coordination mode of the ligand. The biological tests performed with the antibiotic MonH and the corresponding metal(II) complexes show greatly enhanced antimicrobial activity of complexes 2a-b against Gram(+)-bacteria.

First divalent metal complexes of the polyether ionophore Monensin A: X-Ray structures of [Co(Mon)2(H2O)2] and [Mn(Mon)2(H2O)2] and their bactericidal properties.

Abstract In the present paper the synthesis and structural characterization of alkaline-earth metal(II) complexes of the polyether ionophorous antibiotic salinomycinic acid (SalH.H2O) are discussed. The complexes [M(Sal)2(H2O)2] (M = Mg2+, 1; Ca2+, 2; Sr2+, 3; Ba2+, 4) were obtained reacting salinomycinic acid and Et4NOH with the corresponding metal(II) salts at metal-to-ligand-to-base molar ratio of 1:1:1. The spectral properties of 1–4 were characterized using infrared spectroscopy, fast atom bombardment-mass spectrometry, nuclear magnetic resonance and elemental analysis data. The crystallinity degree and morphology of complex 2 were studied by X-ray powder diffraction and transmission electron microscopy. The biometal(II) salinomycinate complexes 1 and 2 possess an enhanced antimicrobial activity compared to the parent antibiotic against Gram-positive bacteria. The comparison between the effectiveness of the complexes, reported here, and the already known isostructural coordination species of salinomycin and monensin (MonH.H2O), revealed that magnesium(II) and calcium(II) monensinates appear to be promising antibacterial agents against Bacillus subtilis, Bacillus cereus and Micrococcus luteus.

Petar Dorkov

Papers

Synthesis, structure and antimicrobial activity of manganese(II) and cobalt(II) complexes of the polyether ionophore antibiotic Sodium Monensin A.

Crystal structure and properties of the copper(II) complex of sodium monensin A.

First divalent metal complexes of the polyether ionophore Monensin A: X-Ray structures of [Co(Mon)2(H2O)2] and [Mn(Mon)2(H2O)2] and their bactericidal properties.

Alkaline-earth metal(II) complexes of salinomycin – spectral properties and antibacterial activity

Mononuclear copper(II) complexes of the macrolide antibiotics tylosin and tilmicosin