Antioxidant and antimicrobial properties of 2-(4,5-dihydro-1H-pyrazol-1-yl)-pyrimidine and 1-carboxamidino-1H-pyrazole derivatives

Five previously synthesized 4-trifluoromethyl-2-(5-aryl-3-styryl-1H-pyrazol-1yl)-pyrimidines and six 5-aryl-3-styryl-1-carboxamidino-1H-pyrazole derivatives were screened for their antioxidant proprieties. The antioxidant activities were evaluated by using the DPPH and the HRP/luminol/H2O2 chemiluminescence assay systems and for their antimicrobial activity (MIC). The results were good for those series in some concentration in comparison with the standards.

A theoretical study of the tautomerism and vibrational spectra of 4,5-diamine-2,6-dimercaptopyrimidine

The 4,5-diamine-2,6-dimercaptopyrimidine (DADMcP) compound is an interesting multifunctional species exhibiting a rather complex tautomerism, encompassing nine tautomeric forms. Investigation of tautomerism in this compound has been carried out by means of FTIR spectroscopy, in association with ab-initio HF/SCF and DFT calculations. According to this study three tautomers are energetically favored; the thione form being the most stable one. The theoretical vibrational spectra of such tautomeric forms have been successfully simulated by means of DFT calculations, allowing the elucidation and assignment of the complex composition of the vibrational bands observed for the mixture of isomers.

Design of 1D and 2D molecule-based magnets with the ligand 4,5-dimethyl-1,2-phenylenebis(oxamato)

Three new bimetallic oxamato-based magnets with the proligand 4,5-dimethyl-1,2-phenylenebis-(oxamato) (dmopba) were synthesized using water or dimethylsulfoxide (DMSO) as solvents. Single crystal X-ray diffraction provided structures for two of them: [MnCu(dmopba)(H(2)O)(3)]n center dot 4nH(2)O (1) and [MnCu(dmopba)(DMSO)(3)](n center dot)nDMSO (2). The crystalline structures for both 1 and 2 consist of linearly ordered oxamato-bridged Mn(II)Cu(II) bimetallic chains. The magnetic characterization revealed a typical behaviour of ferrimagnetic chains for 1 and 2. Least-squares fits of the experimental magnetic data performed in the 300-20 K temperature range led to J(MnCu) = -27.9 cm(-1), g(Cu) = 2.09 and g(Mn) = 1.98 for 1 and J(MnCu) = -30.5 cm(-1), g(Cu) = 2.09 and g(Mn) = 2.02 for 2 (H = -J(MnCu)Sigma S(Mn, i)(S(Cu, i) + S(Cu, i-1))). The two-dimensional ferrimagnetic system [Me(4)N](2n){Co(2)[Cu(dmopba)](3)}center dot 4nDMSO center dot nH(2)O (3) was prepared by reaction of Co(II) ions and an excess of [Cu(dmopba)](2-) in DMSO. The study of the temperature dependence of the magnetic susceptibility as well as the temperature and field dependences of the magnetization revealed a cluster glass-like behaviour for 3.

Hydrogen bonding in 2-(2-oxothiazolidin-3-yl)-4,5-dihydrothiazolium hydrogen sulfate monohydrate

The asymmetric unit of the title compound, C(6)H(9)N(2)OS(2)(+)center dot-HSO(4)(-)center dot H(2)O, contains a heterocyclic cation, a hydrogen sulfate anion and a water molecule. There are strong hydrogen bonds between the hydrogen sulfate anions and water molecules, forming an infinite chain along the [010] direction, from which the cations are pendent. The steric, electronic and geometric features are compared with those of similar compounds. In this way, structural relationships are stated in terms of the influence of the sulfate group on the protonation of the heterocycle and on the tautomeric equilibrium in the solid state.

Antioxidant Capacity of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles

The antioxidant capacity of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles was evaluated. The values of antioxidant capacities of compounds 2d and 2e were found to be, respectively, 2,700 +/- 150 and 3,135 +/- 230 TE by the ORAC method, corresponding to a significant antioxidant capacity.

Efficient sonochemical synthesis of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides

An Ultrasound-assisted preparation of a series of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides that proceeds via the efficient reaction of chalcones with aminoguanidine hydrochloride under clean conditions is described. (C) 2009 Elsevier B.V. All rights reserved.

Environmentally friendly sonocatalysis promoted preparation of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles

An efficient and green synthesis of thiocarbamoyl-3,5-diaryl-4,5-dihydro-1 H-pyrazoles via the condensation of chalcones with thiosemicarbazide in ethanol and KOH under ultrasound irradiation is reported. The products were isolated in good yields after short reaction times. (C) 2009 Elsevier B.V. All rights reserved.

Neuropharmacological effects in mice of Lychnophora species (Vernonieae, Asteraceae) and anticonvulsant activity of 4,5-di-O-[E]-caffeoylquinic acid isolated from the stem of L-rupestris and L-staavioides

Aiming at contributing with the search for neuroactive substances from natural sources, we report for the first time antinociceptive and anticonvulsant effects of some Lychnophora species. We verify the protective effects of polar extracts (600 mg/kg, intraperitoneally), and methanolic fractions of L. staavioides and L. rupestris (100 mg/kg, intraperitoneally) in pentylenetetrazole-induced seizures on mice. Previously, a screening was accomplished, evaluating the antinociceptive central activity (hot plate test), with different extracts of L. rupestris, L. staavioides and L. diamantinana. It was possible to select the possible extracts of Lychnophora with central nervous system activity. Some of the active extracts were submitted to fractionation and purification process and the methanolic fractions of L. rupestris (stem) and L. staavioides (stem), with anticonvulsant properties (100 mg/kg, intraperitoneally), yielded 4,5-di-O-[E]-caffeoylquinic acid. This substance was injected intraperitoneally in mice and showed anticonvulsant effect against pentylenetetrazole-induced seizures at doses of 25 and 50 mg/kg. It has often been shown that seizures induced by pentylenetetrazole are involved in inhibition and/or attenuation of GABAergic neurotransmission. However, other systems of the central nervous system such as adenosinergic and glutamatergic could be involved in the caffeoylquinic acid effects. Further studies should be conducted to verify that the target receptor could be participating in this anticonvulsant property. Although other investigations have reported a series of biological activities from Lychnophora species, this is the first report of central analgesic and anticonvulsant activity in species of this genus.

mRNA differential display of 2-amino-1-methyl-6-phenylinlidazo[4,5-b]pyridine-induced rat mammary gland tumors

The mRNA differential display technique was used to compare mRNAs between normal mammary gland and turner-derived epithelial cells from female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by a high-fat diet (23.5% corn oil). Two genes, beta-casein and transferrin, were identified as differentially expressed. The expression of these genes was examined across a bank of rat mammary gland tumors derived from animals on a low-fat diet (5% corn oil) or the high-fat diet. Carcinomas had over a 10- and 50-fold lower expression of beta-casein and transferrin, respectively than normal mammary gland. In addition, carcinomas from animals on the high-fat diet showed on average a 5-fold higher expression of beta-casein, and transferrin than carcinomas from animals on the low-fat diet. The results indicate the process of mammary gland tumorigenesis alters the expression of certain genes in the mammary gland, and that the level of dietary fat further modulates the expression of these genes.

Characterization of an ATP-dependent pathway of activation for the heterocyclic amine carcinogen N-hydroxy-2-amino-3-methylimidazo[4,5-f]quinoline

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of several mutagenic and carcinogenic heterocyclic amines formed during the cooking process of protein-rich foods, These compounds are highly mutagenic and have been shown to produce tumours in various tissues in rodents and non-human primates. Metabolic activation of IQ is a two-step process involving N-hydroxylation by CYP1A2 followed by esterification to a more reactive species capable of forming adducts with DNA, To date, acetylation and sulphation have been proposed as important pathways in the formation of N-hydroxy esters, In this study we have demonstrated the presence of an ATP-dependent activation pathway for N-hydroxy-IQ (N-OH-IQ) leading to DNA adduct formation measured by covalent binding of [H-3]N-OH-IQ to DNA, ATP-dependent DNA binding of N-OH-IQ was greatest in the cytosolic fraction of rat liver, although significant activity was also seen in colon, pancreas and lung. ATP was able to activate N-OH-IQ almost 10 times faster than N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (7.7 +/- 0.3 and 0.9 +/- 0.1 pmol/mg protein/min, respectively). Using reported intracellular concentrations of cofactor, the ability of ATP to support DNA binding was similar to that seen with 3'-phosphoadenosine 5'-phosphosulphate and similar to 50% of that seen with acetyl coenzyme A (AcCoA), In addition to DNA binding, HPLC analysis of the reaction mixtures using ATP as co-factor showed the presence of two stable, polar metabolites, With AcCoA, only one metabolite was seen. The kinase inhibitors genistein, tyrphostin A25 and rottlerin significantly inhibited both DNA binding and metabolite formation with ATP. However, inhibition was unlikely to be due to effects on enzyme activity since the broad spectrum kinase inhibitor staurosporine had no effect and the inactive analogue of genistein, daidzein, was as potent as genistein, The effects of genistein and daidzein, which are naturally occurring isoflavones from soy and other food products, on DNA adduct formation may potentially be useful in the prevention of heterocyclic amine-induced carcinogenesis.

Characterization of peroxisome proliferator-activated receptor alpha in normal rat mammary gland and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary gland tumors from rats fed high and low fat diets

Normal Sprague-Dau ley rat mammary gland epithelial cells and mammary gland carcinomas induced by 2-amino-1 -methyl-6-phenylimidazo[4,5-b]pyridine, a carcinogen found in the diet, were examined for the expression of peroxisome proliferator-activated receptor alpha (PPAR alpha). PPAR alpha mRNA and protein was detected in normal and tumor tissue by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. By quantitative RT-PCR, carcinomas had a 12-fold higher expression than control mammary glands, a statistically significant difference. PPAR alpha expression was examined in carcinomas and normal tissues from rats on high fat (23.5/% corn oil) and low fat (5% corn oil) diets. Although neither carcinomas, nor control tissues showed statistically significant differences between the two diet groups, PPAR alpha expression was the highest in carcinomas from rats on the high fat diet. The expression of PPAR alpha in normal mammary gland and its significant elevation in mammary gland carcinomas raises the possibility of its involvement in mammary gland physiology and pathophysiology. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.

Arthrodesis of the equine proximal interphalangeal joint: a biomechanical comparison of 3-Hole 4.5 mm locking compression plate and 3-hole 4.5 mm narrow dynamic compression plate, with two transarticular 5.5 mm cortex screws

Objectives To compare the biomechanical characteristics of 2 arthrodesis techniques for the equine proximal interphalangeal joint (PIP) using either a 3-hole 4.5 mm locking compression plate (LCP) or 3-hole 4.5 mm narrow dynamic compression plate (DCP), both with 2 transarticular 5.5 mm cortex screws. Study Design Experimental. Sample Population Cadaveric adult equine forelimbs (*n=6 pairs). Methods For each forelimb pair, 1 limb was randomly assigned to 1 of 2 treatment groups and the contralateral limb by default to the other treatment group. Construct stiffness, gap formation across the PIP joint, and rotation about the PIP joint were determined for each construct before cyclic axial loading and after each of four, 5000 cycle loading regimens. After the 20,000 cycle axial loading regimen, each construct was loaded to failure. Results There were no significant differences in construct stiffness, gap formation, or sagittal plane rotation between the LCP and DCP treatment groups at any of the measured time points. Conclusion Biomechanically, fixation of the equine PIP joint with a 3-hole 4.5 mm LCP is equivalent to fixation with a 3-hole 4.5 mm narrow DCP under the test conditions used.