Silver(I) complexes with voriconazole as promising anti-Candida agents.

Recognizing that metal ions play an important role in modifying the pharmacological properties of known organic-based drugs, the present manuscript addresses the complexation of the antifungal agent voriconazole (vcz) with the biologically relevant silver(I) ion as a strategy for the development of new antimycotics. The synthesized silver(I) complexes with vcz were characterized by mass spectrometry, IR, UV-Vis and NMR spectroscopy and single-crystal X-ray diffraction analysis. The crystallographic results showed that complexes {[Ag(vcz)(HO)]CHSO} (1), {[Ag(vcz)]BF} (2) and {[Ag(vcz)]PF} (3) have polymeric structures in the solid state, in which silver(I) ions have a distorted tetrahedral geometry.

Organometallic Ru(II), Rh(III) and Re(I) complexes of sterane-based bidentate ligands: synthesis, solution speciation, interaction with biomolecules and anticancer activity.

In this study, we present the synthesis, characterization and cytotoxicity of six organometallic [Ru(II)(η--cymene)(,)Cl]Cl, [Rh(III)(η-CMe)(,)Cl]Cl and [Re(I)(CO)(,)Cl] complexes, in which the (,) ligands are sterane-based 2,2'-bipyridine derivatives (4-Me-bpy-St-OH, 4-Ph-bpy-St-OH). The solution chemical behavior of the ligands and the complexes was explored by UV-visible spectrophotometry and H NMR spectroscopy. The ligands and their Re(I) complexes are neutral at pH = 7.

Silver(I) complexes containing antifungal azoles: significant improvement of the anti- potential of the azole drug after its coordination to the silver(I) ion.

Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)]SbF (1, ecz is econazole), {[Ag(vcz)]SbF} (2, vcz is voriconazole), and [Ag(ctz)]SbF (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom.

Investigation of the interaction between S-isoalkyl derivatives of the thiosalicylic acid and human serum albumin.

S-isoalkyl derivatives of thiosalicylic acid (isopropyl-(L1), isobutyl-(L2) and isoamyl-(L3)) were selected in order to investigate the binding interaction with the human serum albumin (HSA) using different spectroscopic methods and molecular docking simulation. Association constants and number of binding sites were used to analyze the quenching mechanism. The experimental results showed that the fluorescence quenching of HSA by L1, L2 and L3 occurs because of static quenching and that binding processes were spontaneous, with the leading forces in bonding by hydrogen bonding, hydrophobic interactions, and electrostatic interactions.

Exploring pta Alternatives in the Development of Ruthenium-Arene Anticancer Compounds.

Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(η--cymene)Ru(pyrithionato)(pta)]PF contains phosphine ligand pta (1,3,5-triaza-7-phosphaadamantane) as a functionality that improves the stability of the complex and its aqueous solubility. Here, we report our efforts to find pta alternatives and discover new structural elements to improve the biological properties of ruthenium anticancer drugs.

Copper(ii) and silver(i) complexes with dimethyl 6-(pyrazine-2-yl)pyridine-3,4-dicarboxylate (py-2pz): the influence of the metal ion on the antimicrobial potential of the complex.

Dimethyl 6-(pyrazine-2-yl)pyridine-3,4-dicarboxylate (py-2pz) was used as a ligand for the synthesis of new copper(ii) and silver(i) complexes, [CuCl(py-2pz)] (1), [Cu(CFSO)(HO)(py-2pz)]CFSO·2HO (2), [Ag(py-2pz)]PF (3) and {[Ag(NO)(py-2pz)]·0.5HO} (4). The complexes were characterized by spectroscopic and electrochemical methods, while their structures were determined by single crystal X-ray diffraction analysis.

Ruthenium complexes show potent inhibition of AKR1C1, AKR1C2, and AKR1C3 enzymes and anti-proliferative action against chemoresistant ovarian cancer cell line.

In this study, we present the synthesis, kinetic studies of inhibitory activity toward aldo-keto reductase 1C (AKR1C) enzymes, and anticancer potential toward chemoresistant ovarian cancer of 10 organoruthenium compounds bearing diketonate (-) and hydroxyquinolinate (-) chelating ligands with the general formula [(η--cymene)Ru(chel)(X)] where chel represents the chelating ligand and X the chlorido or pta ligand. Our studies show that these compounds are potent inhibitors of the AKR enzymes with an uncommon inhibitory mechanism, where two inhibitor molecules bind to the enzyme in a first fast and reversible step and a second slower and irreversible step. The binding potency of each step is dependent on the chemical structure of the monodentate ligands in the metalloinhibitors with the chlorido complexes generally acting as reversible inhibitors and pta complexes as irreversible inhibitors.

Kinetic Characterization of Cerium and Gallium Ions as Inhibitors of Cysteine Cathepsins L, K, and S.

Heavy metal ions can disrupt biological functions via multiple molecular mechanisms, including inhibition of enzymes. We investigate the interactions of human papain-like cysteine endopeptidases cathepsins L, K, and S with gallium and cerium ions, which are associated with medical applications. We compare these results with zinc and lead, which are known to inhibit thiol enzymes.

Zinc pyrithione is a potent inhibitor of PL and cathepsin L enzymes with inhibition of SARS-CoV-2 entry and replication.

Zinc pyrithione (), together with its analogues - and ruthenium pyrithione complex , were synthesised and evaluated for the stability in biologically relevant media and anti-SARS-CoV-2 activity. Zinc pyrithione revealed potent inhibition of cathepsin L (IC=1.88 ± 0.

Metal(II) Complexes of the Fluoroquinolone Fleroxacin: Synthesis, Characterization and Biological Profile.

A series of complexes of divalent transition metals (Cu(II), Mn(II), Zn(II), Co(II) and Ni(II)) with the quinolone antibacterial agent fleroxacin, in the absence or presence of an -diimine such as 2,2'-bipyridine, 1,10-phenanthroline or 2,2'-bipyridylamine, were prepared and characterized. The complexes were characterized by various physicochemical and spectroscopic techniques and by single-crystal X-ray crystallography. The in vitro antibacterial activity of the complexes was studied against the bacterial strains , and and was higher than that of free quinolone.

Clinically used antifungal azoles as ligands for gold(III) complexes: the influence of the Au(III) ion on the antimicrobial activity of the complex.

In a search for novel antimicrobial metal-based therapeutic agents, mononuclear gold(III) complexes 1-7 of the general formula [AuCl(azole)], where azole stands for imidazole (im, 1), 1-isopropylimidazole (ipim, 2), 1-phenylimidazole (phim, 3), clotrimazole (ctz, 4), econazole (ecz, 5), tioconazole (tcz, 6) and voriconazole (vcz, 7) were synthesized, characterized and biologically evaluated. In all complexes, the corresponding azole ligand is monodentately coordinated to the Au(III) the imidazole or triazole nitrogen atom, while the remaining coordination sites are occupied by chloride anions leading to the square-planar arrangement. antimicrobial assays showed that the complexation of inactive azoles, imidazole, 1-isopropylimidazole and 1-phenylimidazole, to the Au(III) ion led to complexes 1-3, respectively, with moderate activity against the investigated strains and low cytotoxicity on the human normal lung fibroblast cell line (MRC-5).

Platinum(II) complexes with malonic acids: Synthesis, characterization, in vitro and in vivo antitumor activity and interactions with biomolecules.

Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is an anion of either malonic acid (mal, Pt1), 2-methylmalonic acid (Me-mal, Pt2), 2,2-dimethylmalonic acid (Me-mal, Pt3) or 1,1-cyclobutanedicarboxylic acid (CBDCA, Pt4) and 5,6-epoxy-1,10-phen is 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, were synthesized and characterized by elemental microanalysis and different spectroscopic techniques. The crystal structure of anhydrous Pt3 complex was determined by single crystal X-ray diffraction. The in vitro anticancer activity of the platinum(II) complexes was investigated in human and murine cancer cell lines as well as in a normal murine cell line by MTT assay.

Comparison of Solution Chemical Properties and Biological Activity of Ruthenium Complexes of Selected -Diketone, 8-Hydroxyquinoline and Pyrithione Ligands.

In this work, the various biological activities of eight organoruthenium(II) complexes were evaluated to reveal correlations with their stability and reactivity in aqueous media. Complexes with general formula [Ru(η--cymene)(X,Y)(Z)] were prepared, where (X,Y) represents either an ,-ligand (-diketone), ,-ligand (8-hydroxyquinoline) or ,-pyrithione-type ligands (pyrithione = 1-hydroxypyridine-2(1)-thione) with Cl or 1,3,5-triaza-7-phosphaadamantane (PTA) as a co-ligand (Z). The tested complexes inhibit the chlamydial growth on HeLa cells, and one of the complexes inhibits the growth of the human herpes simplex virus-2.

Organoruthenium Complexes with Benzo-Fused Pyrithiones Overcome Platinum Resistance in Ovarian Cancer Cells.

Drug resistance to existing anticancer agents is a growing clinical concern, with many first line treatments showing poor efficacy in treatment plans of some cancers. Resistance to platinum agents, such as cisplatin, is particularly prevalent in the treatment of ovarian cancer, one of the most common cancers amongst women in the developing world. Therefore, there is an urgent need to develop next generation of anticancer agents which can overcome resistance to existing therapies.

Structure of Biologically Active Benzoxazoles: Crystallography and DFT Studies.

Using X-ray single crystal diffraction, the crystal structures of biologically active benzoxazole derivatives were determined. DFT calculation was performed with standard 6-31G*(d), 6-31G** and 6-31+G* basis set to analyze the molecular geometry and compare with experimentally obtained X-ray crystal data of compounds. The calculated HOMO-LUMO energy gap in compound 2 (2-(2-hydroxynaphtalen-1-yl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol) is 3.

Tailoring copper(ii) complexes with pyridine-4,5-dicarboxylate esters for anti-Candida activity.

Five novel copper(ii) complexes with pyridine-4,5-dicarboxylate esters as ligands, [Cu(NO)(py-2tz)(HO)]NO (1), [Cu(NO)(py-2metz)(HO)] (2), [Cu(NO)(py-2py)(HO)]·HO (3), [CuCl(py-2tz)] (4) and [CuCl(py-2metz)] (5) (py-2tz is dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate, py-2metz is dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate and py-2py is dimethyl 2,2'-bipyridine-4,5-dicarboxylate), were synthesized and structurally characterized by different spectroscopic and electrochemical methods. The structure of these complexes was determined by single-crystal X-ray diffraction analysis, confirming the bidentate coordination mode of the corresponding pyridine-4,5-dicarboxylate ester to the Cu(ii) ion through the nitrogen atoms. The antimicrobial potential of copper(ii) complexes 1-5 was assessed against two bacterial and two Candida species.

Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential.

Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl(fcz)]5HO}, , and {[ZnCl(fcz)]·2CHOH}, , were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises four fluconazole molecules monodentately coordinated via the triazole nitrogen and two chlorido ligands. With respect to fluconazole, complex showed significantly higher antifungal activity against and .

Structural Isomerism and Enhanced Lipophilicity of Pyrithione Ligands of Organoruthenium(II) Complexes Increase Inhibition on AChE and BuChE.

The increasing number of Alzheimer's disease (AD) cases requires the development of new improved drug candidates, possessing the ability of more efficient treatment as well as less unwanted side effects. Cholinesterase enzymes are highly associated with the development of AD and thus represent important druggable targets. Therefore, we have synthesized eight organoruthenium(II) chlorido complexes - with pyrithione-type ligands (pyrithione = 1-hydroxypyridine-2(1)-thione, ), bearing either pyrithione , its methyl (-) or bicyclic aromatic analogues (-) and tested them for their inhibition towards electric eel acetylcholinesterase (eeAChE) and horse serum butyrylcholinesterase (hsBuChE).

Structural and functional characterization of an organometallic ruthenium complex as a potential myorelaxant drug.

In addition to antibacterial and antitumor effects, synthetic ruthenium complexes have been reported to inhibit several medicinally important enzymes, including acetylcholinesterase (AChE). They may also interact with muscle-type nicotinic acetylcholine receptors (nAChRs) and thus affect the neuromuscular transmission and muscle function. In the present study, the effects of the organometallic ruthenium complex of 5-nitro-1,10-phenanthroline (nitrophen) were evaluated on these systems.

Silver(i) complexes with different pyridine-4,5-dicarboxylate ligands as efficient agents for the control of cow mastitis associated pathogens.

Infections of the cow udder leading to mastitis and lower milk quality are one of the biggest problems in the dairy industry worldwide. Unfortunately, therapeutic options for the treatment of cow mastitis are limited as a consequence of the development of pathogens that are resistant to conventionally used antibiotics. In the search for agents that will be active against cow mastitis associated pathogens, in the present study, five new silver(i) complexes with different chelating pyridine-4,5-dicarboxylate types of ligands, [Ag(NO)(py-2py)] (1), [Ag(NO)(py-2metz)] (2), [Ag(CHCN)(py-2py)]BF (3), [Ag(py-2tz)]BF (4) and [Ag(py-2metz)]BF (5), py-2py is dimethyl 2,2'-bipyridine-4,5-dicarboxylate, py-2metz is dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate and py-2tz is dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate, were synthesized, structurally characterized and assessed for in vitro antimicrobial activity using both standard bioassay and clinical isolates from a contaminated milk sample obtained from a cow with mastitis.

Organoruthenated Nitroxoline Derivatives Impair Tumor Cell Invasion through Inhibition of Cathepsin B Activity.

Lysosomal cysteine peptidase cathepsin B (catB) is an important tumor-promoting factor involved in tumor progression and metastasis representing a relevant target for the development of new antitumor agents. In the present study, we synthesized 11 ruthenium compounds bearing either the clinical agent nitroxoline that was previously identified as potent selective reversible inhibitor of catB activity or its derivatives. We demonstrated that organoruthenation is a viable strategy for obtaining highly effective and specific inhibitors of catB endo- and exopeptidase activity, as shown using enzyme kinetics and microscale thermophoresis.

Towards Identification of Essential Structural Elements of Organoruthenium(II)-Pyrithionato Complexes for Anticancer Activity.

An organoruthenium(II) complex with pyrithione (2-mercaptopyridine N-oxide) 1 a has previously been identified by our group as a compound with promising anticancer potential without cytotoxicity towards non-cancerous cells. To expand the rather limited research on compounds of this type, an array of novel chlorido and 1,3,5-triaza-7-phosphaadamantane (pta) organoruthenium(II) complexes with methyl-substituted pyrithiones has been prepared. After thorough investigation of the aqueous stability of these complexes, their modes of action have been elucidated at the cellular level.

Covalent versus Noncovalent Binding of Ruthenium η -p-Cymene Complexes to Zinc-Finger Protein NCp7.

Ruthenium-arene complexes are a unique class of organometallic compounds that have been shown to have prominent therapeutic potencies. Here, we have investigated the interactions of Ru-cymene complexes with a zinc-finger protein NCp7, aiming to understand the effects of various ligands on the reaction. Five different binding modes were observed on selected Ru-complexes.

Comparative antitumor studies of organoruthenium complexes with 8-hydroxyquinolines on 2D and 3D cell models of bone, lung and breast cancer.

The purpose of this work was to screen the antitumor actions of two metal organoruthenium-8-hydroxyquinolinato (Ru-hq) complexes to find a potential novel agent for bone, lung and breast chemotherapies. We showed that ruthenium compounds (1 and 2) impaired the cell viability of human bone (MG-63), lung (A549) and breast (MCF7) cancer cells with greater selectivity and specificity than cisplatin. Besides, complexes 1 and 2 decreased proliferation, migration and invasion on cell monolayers at lower concentrations (2.