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Metal complexes, which, under physiologic conditions, show redox properties and are able to bind to DNA, are great tools to cleave the DNA chain. This aspect is of great importance for their use as antineoplastic drugs. We synthesized ligands derived from short-chain amino acids and from salicylaldehyde. The prepared ligands of the type of reduced Schiff bases were subsequently used for the preparation of copper(II) complexes. The aim of the study was in vitro testing of copper(II) complexes, where it was confirmed that they are capable of cleaving DNA. Their cytotoxic activity was also confirmed by the resazurin redox method on Saccharomyces cerevisiae based on preserved healthy mitochondrial function.

Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring—the dichloro[(±)-trans-N,N′-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC50 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC50 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC50 values in the lower micromolar region. [ABSTRACT FROM AUTHOR]

Metal complexes, which, under physiologic conditions, show redox properties and are able to bind to DNA, are great tools to cleave the DNA chain. This aspect is of great importance for their use as antineoplastic drugs. We synthesized ligands derived from short-chain amino acids and from salicylaldehyde. The prepared ligands of the type of reduced Schiff bases were subsequently used for the preparation of copper(II) complexes. The aim of the study was in vitro testing of copper(II) complexes, where it was confirmed that they are capable of cleaving DNA. Their cytotoxic activity was also confirmed by the resazurin redox method on Saccharomyces cerevisiae based on preserved healthy mitochondrial function. [ABSTRACT FROM AUTHOR]

So far, the polyphenolic components of turmeric have shown a significant pharmacological preventative activity for a wide spectrum of diseases, including oncological disorders. This type of natural product could be of great interest for the inhibition of cancer cell proliferation, displaying less side effects in comparison to classical chemotherapeutics. The poor bioavailability and quick metabolism of such natural compounds require new investigative methods to improve their stability in the organisms. A synthetic approach to increase the efficiency of curcuminoids is to coordinate them to metals through the beta-dicarbonyl moiety. We report the synthesis and the biological attempts on human ovarian carcinoma A2780 of ruthenium(II) complexes 1–4, containing curcuminoid ligands. The cytotoxicity of complexes 1–4 proves their antiproliferative capability, and a correlation between the IC50 values and NF-κB transcription factor, FGF-2, and MMP-9 levels was figured out through the principal component analysis (PCA). [ABSTRACT FROM AUTHOR]

Superoxide dismutases (SOD) are a group of metallo-enzymes, containing one or two coordinated metals, and their main role in the organism is protection against superoxide radicals, one of the reactive oxygen species (ROS). Among these Cu(II)-Zn(II) SOD is present in cytoplasm and acts as a scavenger of superoxide radicals. Cu(II)-complexes may act as low-molecule analogue of Cu-Zn SOD and therefore are being studied as antiradical agents. In this study a series of Cu(II) complexes were synthesizes, containing ligands prepared from salicyl aldehyde and amino acids: L-asparagine, L-glutamine and L-aspartic acid. Complexes prepared from L-asparagine and L-glutamine are novel and were compared with the already reported complex Cu(HSal-L-Asp) hydrate (6e). An assay based on the ability to inhibit reduction of iodonitrotetrazolium dye (INT) by superoxide anion-radicals was used to determine antiradical activity of these complex. The prepared complexes - Cu(HSal-L-Asn) acetate (6a), Cu(HSal-L-Asn) hydrate (6b) and Cu(HSal-L-Gln) acetate (6c) proved to be good antiradical agents compared to complex 6e. The IC50 values of the radical transport were 19.2 ± 1.2 μM for 6a, 53.9 ± 9.4 μM for 6b and 4.11 ± 0.37 mM for 6c. [ABSTRACT FROM AUTHOR]

The iron heterometallic trimeric clusters constitute a broad field for research, as shown by a recent survey covering the crystallographic and structural parameters of over 600 examples. About 7.5% of these clusters exist as distortion isomers and are summarized. These are discussed in terms of the coordination about the metal atoms, bond lengths and interbond angles. Only distortion isomers cover all the mentioned clusters. Distortion isomers differ mostly by degree of distortion in M-L, M-L-M and L-M-L parameters. There are 15 metal partners with the iron atom, with three categories of trimers (Fe2M(x18), FeM2(x19) and FeMM´(x4)). The shortest metal-metal bond distances are: 2.504(1) Å (Fe-Fe), 2.368(1) Å (Fe-Ni), and 2.288(1) Å (W-W). From the structural point of view, a triangular core of the metal atoms capped by  3-X (X=S, Cl or PL) is the most common. [ABSTRACT FROM AUTHOR]

The present paper reports the synthesis of a series of seven compounds with a hetero aminopropanol chain. The compounds were prepared by the conversion of 3-alkoxy-4-hydroxyphenyl alkanones with 2-chloromethyl oxirane and subsequent reaction of the products with heterocyclic amines (pyrrolidine, azepane, 4-methylpiperazine and 2-methoxyphenyl piperazine). The target compounds were synthesized in the form of racemates. The purity of the products was confirmed by thin layer chromatography and their IR, UV-VIS and 1H-NMR spectra were recorded. Enantioseparation of the racemic products was accomplished by HPLC on a Chiralpak AD chiral chromatographic column with tris(3,5-dimethylphenyl)carbamate as the chiral selector. The efficiency of enantioseparation was determined in relation to the composition of the mobile phase (hexane : ethanol : methanol : ethylethanamine) and to the structure of the prepared compounds. Baseline separation was achieved with all compounds using mobile phases A (78 : 11 : 11 : 0,1 v/v/v/v) and B (80 : 10 : 10 : 0,1 v/v/v/v), with selectivity factor ranging from 1.07 to 1.42 and resolution from 0.76 to 5.47. The mobile phase containing a higher amount of hexane did not allow for successful enantioseparation of the piperazine derivatives.

Therapy of malignant tumors is among the oldest and at the same time the most promising application areas of therapeutic metal complexes. The second part of our survey on metallopharmaceuticals deals with historical development and current state of coordination compounds in cancer therapy. It starts with the most famous and most successful metallodrug - cisplatin. After a brief account of the discovery of the anticancer properties of this substance follows the discussion of its chemical properties, toxicity, clinical application and resistance. Hereafter, complexes of other metals along with innovative research directions are addressed. The aim of this brief survey is to provide basic overview of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public.

Metals and their compounds have been exploited in medicine since the dawn of history. All metals (or their substances) exert some kind of biological activity. Metal complexes exhibit a number of unique properties as compared to purely organic substances, stemming from the presence of the metal atom and the variable arrangement of ligands around this central atom. The goal of this brief survey is to provide basic overview of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public. The first part concentrates on some historical aspects of metallopharmacy and on current application of metals in the therapy of infectious diseases and in diagnostics.

Objectives: A stereoselective HPLC method was developed to separate and quantify both enantiomers of methadone and its main metabolite EDDP in serum and urine. The method was used to establish that there is a relationship between the dose of methadone prescribed and its serum concentration as well as urine excretion of methadone and its metabolite enantiomers., Methods: The chiral alpha1-glycoprotein stationary phase was used for enantioseparation of (R)-methadone, (S)-methadone and (R)-EDDP (S)-EDDP. The enantiomers of methadone and EDDP were extracted from urine and serum by a simple solidphase procedure., Results: The validated method was applied to the analysis of 31 serum and urine samples obtained from methadone-maintained outpatients (65% male, age 28.8+/-4; methadone dose 146+/-47 mg). A significant correlation (Pearson) r=0.67 (p<0.001) between methadone dose and serum concentration of (R)-methadone was found. Due to the large variation in results obtained from analysis of the subjects' urine specimens, no statistically significant relationship between methadone dose and urine excretion of methadone and EDDP enantiomers was established. The rate of R/S methadone (1.38 in serum, 2.43 in urine) and R/S EDDP (0.83 in urine) confirmed stereoselectivity in methadone metabolism with high individual variability., Conclusions: The enantioselective evaluation of serum methadone concentration might be an interesting tool in methadone maintenance programme. On the other hand, the urinary excretion of methadone and EDDP enantiomers is not reliable as marker of methadone compliance but could be useful for monitoring individual metabolism or for studying the stereoselectivity in pharmacokinetics and metabolism of methadone.

Objectives: Lipoxygenases (EC 1.13.11.12, LOX) catalyze the hydroperoxidation of polyunsaturated fatty acids (PUFA). This reaction leads to the production of conjugated hydro peroxide dienes of PUFA. In animals, LOX generate leukotriens (LT) and lipoxins, which belong to inflammatory mediators. It is believed that restricting LT synthesis by inhibition of LOX would have therapeutic utility for the treatment of a variety of inflammatory conditions (e.g. asthma, rheumatoid arthritis, psoriasis)., Methods & Results: The process of production and elimination of radical intermediates in vitro can be monitored by determination of LOX activity. We assessed the concentration of PUFA hydroperoxides in our system with LOX-catalyzed enzyme reaction spectrophotometrically. The inhibition of LOX activity (LOX from cytosol fraction of rat lungs) with selected N-salicylideneaminoalkanoatocopper(II) complexes was tested. In our experiments, all compounds tested showed an inhibitory effect on LOX catalyzed hydroperoxidation of PUFA. Cu(II) (from CuSO(4).5H(2)O dilution) ions also inhibited this enzyme reaction, but all compounds studied had a 10 times higher anti-LOX activity. The most effective of these complexes was monohydrate aqua-(N-salicylidene-L-a-alaninato)copper(II) complex [Cu(sal-L-alpha-ala)(H(2)O)].H(2)O with IC(50) 1.86 x 10(-4) mol/l., Conclusions: These complexes are known for their anti-phlogistic and radioprotective properties and they can be classified as potential anti-radical compounds. The structure of these complexes is similar to the active site of Cu,Zn-SOD (superoxide dismutase) and superoxide radical scavenger activity of these complexes is known. We found that these copper complexes were capable to inhibit LOX activity, which may be related with their anti-radical properties.