salicylates and 1-10-phenanthroline

Silver complexes containing 1,10-phenanthroline as a coordinated ligand have been of great interest due to their antibacterial and antifungal pharmacological properties. In this paper, we describe the synthesis of a new partial inclusion complex of bis(1,10-phenanthroline)silver(I) salicylate in β-cyclodextrin (β-CD) which was synthesized with a good yield. The compounds were characterized by FTIR, 1H, 13C NMR including 1H-1H COSY, TGA/DSC, elemental analysis (CHN), and X-ray powder diffraction. The results suggest the presence of non-covalent interactions such as hydrogen bonds, van der Waals forces, and hydrophobic interactions in the formation of the partial inclusion compound between β-CD and bis(1,10-phenanthroline)silver(I) salicylate [Ag(phen)2]salH. Additionally, an in silico prediction of 1,10-phenanthroline biological activities was carried out and the acquired data suggests several potential targets associated with the antimicrobial activity of this compound and its silver complex. Most predicted targets are related to antimicrobial virulence and resistance that are a serious threat to global public health. The inclusion compound showed a higher inhibiting growth of Candida albicans than the free complex [Ag(phen)2]salH indicating that the formation of the inclusion complex with β-CD increases the bioavailability of the antimicrobial active species [Ag(phen)2]+ of the new silver(I) compound.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; beta-Cyclodextrins; Computer Simulation; Phenanthrolines; Salicylates; Silver

In this study, we investigated anti-tumor activity and associated molecular mechanism of action of Salicylate ●Phenanthroline Copper (II) Complex in triple-negative breast cancer. Salicylate ●Phenanthroline Copper (II) Complex inhibited the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20) and induced apoptosis in a concentration-dependent manner. The effect was more profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines. Western blot showed that the expression of the apoptosis-related protein Bcl-2, Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with Salicylate ●Phenanthroline Copper (II) Complex. In vivo, Salicylate ●Phenanthroline Copper (II) Complex administration significantly attenuated tumor growth of MDA-MB-231 xenografts, and the expression levels of Bcl-2, Bcl-xL and survivin were reduced as measured by immunohistochemical staining. These data suggest that Salicylate ●Phenanthroline Copper (II) Complex is a promising novel therapeutic drug for triple-negative breast cancer and warrants further study.

Topics: Animals; Antineoplastic Agents; Apoptosis; Biomarkers; Cell Line, Tumor; Disease Models, Animal; Female; Humans; Mice; Organometallic Compounds; Phenanthrolines; Salicylates; Triple Negative Breast Neoplasms; Xenograft Model Antitumor Assays

Two novel palladium(II) complexes with a thiosalicylic acid (HSC(6)H(4)CO(2)H) ligand, with the formulas [Pd(TSA)(L)]·mH(2)O (TSA is thiosalicylic acid; in complex 1, L is 1,10-phenanthroline and m = 1; in complex 2, L is 2,2'-bipyridine and m = 2), have been synthesized and characterized. The coordination geometry of both palladium atoms is square planar; they are four-coordinated and each is coordinated in an N,N,O(-),S(-) mode. There is a sigmoid oxygen chain in complex 1, but an oxygen ring in complex 2. The competitive binding of the complexes to HeLa cell DNA (HL-DNA) has been investigated by fluorescence spectroscopy. The results show that the two complexes have the ability to bind with HL-DNA. Viscosity studies suggest that the complexes bind to DNA by intercalation. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the HL-DNA. The two complexes exhibit cytotoxic specificity and a significant cancer cell inhibitory rate. The apoptosis tests indicated that the complexes have an apoptotic effect. Furthermore, complex 1 exhibits more biological activity than complex 2, which is mainly because the area of the aromatic ring of 1,10-phenanthroline is larger than that of 2,2'-bipyridine.

Topics: 2,2'-Dipyridyl; Antineoplastic Agents; Apoptosis; DNA; HeLa Cells; Humans; Intercalating Agents; Ligands; Neoplasms; Palladium; Phenanthrolines; Salicylates; Sulfhydryl Compounds; Sulfur

The title compounds, bis(μ-3,5-dichloro-2-oxidobenzoato)-κ(3)O(1),O(2):O(2);κ(3)O(2):O(1),O(2)-bis[(3,5-dichloro-2-hydroxybenzoic acid-κO(1))(1,10-phenanthroline-κ(2)N,N')copper(II)], [Cu(2)(C(7)H(2)Cl(2)O(3))(2)(C(7)H(4)Cl(2)O(3))(2)(C(12)H(8)N(2))(2)], (I), and bis(μ-5-chloro-2-oxidobenzoato)-κ(3)O(1),O(2):O(1);κ(3)O(1):O(1),O(2)-bis[(5-chloro-2-hydroxybenzoic acid-κO(1))(1,10-phenanthroline-κ(2)N,N')copper(II)] ethanol monosolvate, [Cu(2)(C(7)H(3)ClO(3))(2)(C(7)H(5)ClO(3))(2)(C(12)H(8)N(2))(2)]·C(2)H(6)O, (II), contain centrosymmetric dinuclear complex molecules in which Cu(2+) cations are surrounded by a chelating 1,10-phenanthroline ligand, a chelating 3,5-dichloro-2-oxidobenzoate or 5-chloro-2-oxidobenzoate anionic ligand and a monodentate 3,5-dichloro-2-hydroxybenzoic acid or 5-chloro-2-hydroxybenzoic acid ligand. The chelating benzoate ligand also bridges to the other Cu(2+) ion in the molecule, but the O atom involved in the bridge is different in the two complexes, being the phenolate O atom in (I) and a carboxylate O atom in (II). The bridge completes a 4+1+1 axially elongated tetragonal-bipyramidal arrangement about each Cu(2+) cation. The complex molecules of both compounds are linked into one-dimensional supramolecular chains through O-H...O hydrogen bonds.

Topics: Chlorobenzenes; Chlorobenzoates; Copper; Crystallography, X-Ray; Hydroxybenzoates; Models, Molecular; Molecular Structure; Phenanthrolines; Salicylates; Stereoisomerism

The method exploits the possibilities of flow injection gradient titration in a system of reversed flow with spectrophotometric detection. In the developed approach a small amount of titrant (EDTA) is injected into a stream of sample containing a mixture of indicators (sulfosalicylic acid and 1,10-phenanthroline). In acid environment sulfosalicylic acid forms a complex with Fe(III), whereas 1,10-phenanthroline forms a complex with Fe(II). Measurements are performed at wavelength lambda=530 nm when radiation is absorbed by both complexes. After injection EDTA replaces sulfosalicylic acid and forms with Fe(III) more stable colourless complex. As a result, a characteristic "cut off" peak is registered with a width corresponding to the Fe(III) concentration and with a height corresponding to the Fe(II) concentration. Calibration was performed by titration of four two-component standard solutions of the Fe(II)/Fe(III) concentrations established in accordance with 2(2) factorial plan. The method was tested with the use of synthetic samples and then it was applied to the analysis of water samples taken from artesian wells. Under optimized experimental conditions Fe(II) and Fe(III) were determined with precision less than 0.8 and 2.5% (RSD) and accuracy less than 3.2 and 5.1% (relative error) within the concentration ranges of 0.1-3.0 and 0.9-3.5 mg L(-1) of both analytes, respectively.

Topics: Benzenesulfonates; Calibration; Ferric Compounds; Ferrous Compounds; Flow Injection Analysis; Fresh Water; Phenanthrolines; Salicylates; Spectrophotometry, Ultraviolet

Two ternary Cu(II) complexes of 1,10-phenanthroline (phen) and singly (Hsal(-)) or dideprotonated (sal(2-)) salicylate ligands were synthesized, their X-ray crystal structure and electron paramagnetic resonance spectral characteristics determined, and evaluated for anti-convulsant activities in the maximal electroshock (MES) and Metrazol models of seizure and Rotorod toxicity. The X-ray crystal structure of [bis(1,10-phenanthroline)-mu-bis(salicylato-O,O')dicopper(II)] dihydrate, 1, ([Cu(II)(2)(phen)(2)(sal)(2)].2[H(2)O]), shows it to be binuclear. This dimer consists of two centrosymmetrically related pseudo-five coordinate Cu(II) atoms 3.242(2) A apart and bridged by two dideprotonated salicylate ligands. The X-ray crystal structure of [bis(1,10-phenanthroline)(salicylato)copper(II)][salicylate] monohydrate, 2, ([Cu(II)(phen)(2)(Hsal)](+)[Hsal](-)[H(2)O]), shows it to be mononuclear. This complex cation exhibits a highly irregular distorted square pyramidal geometry about the Cu(II) atom, (4+1+1*). Each salicylate is singly deprotonated and one of them is ligand bonded in an asymmetric chelating mode. EPR results for 2 indicate that in concentrated DMF solution phen remains bonded to copper but salicylate is likely monodentate in contrast to the situation for 1. However, in dilute DMF solution, both 1 and 2 form the same species, which accounts for the similarity in anti-convulsant activity of the two compounds. Both 1 and 2 were found to be effective in preventing MES-induced seizures and ineffective in preventing Metrazol-induced seizures. Rotorod toxicity, consistent with central nervous system depression, paralleled the observed anti-convulsant activity. It is suggested that the observed anti-convulsant activity is consistent with central nervous system depression as a physiological mechanism in overcoming MES-induced seizures due to MES-induced brain inflammatory disease.

Topics: Animals; Anticonvulsants; Cations, Divalent; Central Nervous System; Copper; Crystallography, X-Ray; Electron Spin Resonance Spectroscopy; Hydrogen Bonding; Magnetics; Mice; Models, Molecular; Molecular Conformation; Phenanthrolines; Rats; Salicylates; Spectrophotometry, Atomic; Structure-Activity Relationship

The model quinone compound menadione has been used to study the effects of oxidative stress in mammalian cells, and to investigate the mechanism of action of the quinone nucleus which is present in many anti-cancer drugs. We have used the alkaline single cell gel electrophoresis assay (comet assay) to investigate the effects of low doses of this compound on isolated human lymphocytes. We found that concentrations of menadione as low as 1 microM were sufficient to induce strand breaks in these cells. Pre-incubation with the NAD(P)H quinone oxidoreductase inhibitor dicoumarol, enhanced the production of menadione-induced strand breaks. In contrast, the metal ion chelator 1,10-phenanthroline inhibited formation of strand breaks, although prolonged incubation with 1,10-phenanthroline in combination with menadione resulted in an increase in a population of very severely damaged nuclei. A marked variation in the response of lymphocytes from different donors to menadione, and in different samples from the same donor was also observed.

Topics: Antioxidants; Ascorbic Acid; Cell Survival; Chelating Agents; Dicumarol; Dimethyl Sulfoxide; DNA Damage; DNA Fragmentation; Electrophoresis, Agar Gel; Enzyme Inhibitors; Humans; Lymphocytes; Male; NAD(P)H Dehydrogenase (Quinone); Oxidative Stress; Phenanthrolines; Salicylates; Salicylic Acid; Vitamin K

The genotoxic/mutagenic mechanism(s) of action of fecapentaene-12 (fec-12) is complex but there is evidence to suggest that the generation of active oxygen species (AOS) may be involved. This has been assessed by measuring the formation of 8-hydroxydeoxyguanosine (8-OHdG) in isolated DNA and HeLa cells exposed in vitro to fec-12. The possibility that fec-12 may form AOS via peroxidative 'activation' by prostaglandin H synthase (PHS) has been investigated by measuring 8-OHdG in HeLa cells exposed to fec-12 in the absence or presence of PHS inhibitors. The role of iron as a catalyst in this pathway has also been investigated. A 4-fold increase in the level of 8-OHdG in isolated DNA was seen after exposure to fec-12 (1 mM) alone. This increase was enhanced synergistically by ferrous iron. Fec-12 exposure of HeLa cells at 50 and 100 microM induced 2- and 3-fold increases (P < 0.001) respectively in the level of 8-OHdG in cellular DNA. No increase was seen at 10 microM fec-12. The PHS inhibitors indomethacin and acetylsalicylate blocked the formation of 8-OHdG induced by fec-12 (50 microM) but did not inhibit the formation of 8-OHdG in these cells after exposure to H2O2 and Fe2+. Addition of the iron chelating agent o-phenanthroline to cells prior to fec-12 exposure blocked the increase in 8-OHdG induced by fec-12 (50 microM). Addition of the radical scavenging agent DMSO (10%) to cells prior to fec-12 exposure reduced the level of 8-OHdG to within 10% of control. Specific inhibition of fec-12 induced 8-OHdG formation in HeLa cells by PHS inhibitors suggests that this enzyme may be involved in 'activating' fec-12 to form AOS in cells. Inhibition of fec-12 induced 8-OHdG formation in cells by o-phenanthroline suggests a role for intracellular iron as a catalyst in this process.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Cyclooxygenase Inhibitors; Deoxyguanosine; DNA; HeLa Cells; Humans; Indomethacin; Phenanthrolines; Polyenes; Salicylates

When Chinese hamster fibroblasts were exposed to hydrogen peroxide or to a system consisting of xanthine oxidase and hypoxanthine, which generates superoxide anion plus hydrogen peroxide, sister-chromatid exchanges (SCEs) were formed in a dose-dependent manner. When the iron-complexing agent o-phenanthroline was present in the medium, however, the production of these SCEs was completely inhibited. This fact indicates that the Fenton reaction: Fe2+ + H2O2----OH0 + OH- + Fe3+ is responsible for the production of SCEs. When O2- and H2O2 were generated inside the cell by incubation with menadione, the production of SCE was prevented by co-incubation with copper diisopropylsalicylate, a superoxide dismutase mimetic agent. The most likely role of O2- is as a reducing agent of Fe3+: O2- + Fe3+----Fe2+ + O2, so that the sum of this and the Fenton reaction, i.e., the iron-catalyzed Haber-Weiss reaction, provides an explanation for the active oxygen species-induced SCE: H2O2 + O2(-)----OH- + OH0 + O2. According to this view, the OH radical thus produced is the agent which ultimately causes SCE. These results are discussed in comparison with other mechanisms previously proposed for induction of SCE by active oxygen species.

Topics: Animals; Cell Cycle; Cell Line; Cricetinae; Drug Synergism; Free Radicals; Hydrogen Peroxide; Hydroxides; Iron; Phenanthrolines; Salicylates; Sister Chromatid Exchange; Superoxides; Vitamin K