Evaluation of anti-inflammatory activity of derivatives from aerial parts of Baccharis uncinella

Context: Species of Baccharis exhibit antibiotic, antiseptic, and wound-healing properties, and have been used in the traditional medicine of South America for the treatment of inflammation, headaches, diabetes, and hepatobiliary disorders. Objective: To investigate the anti-inflammatory activity of organic phases from EtOH extract of the aerial parts of Baccharis uncinella DC (Asteraceae). Materials and methods: The crude EtOH extract from the aerial parts of B. uncinella was subjected to partition procedures and the corresponding CH(2)Cl(2) and EtOAc phases were subjected to several chromatographic separation procedures. Thus, these phases and their purified compounds were assayed for evaluation of anti-inflammatory activity. Results: The CH(2)Cl(2) phase from EtOH extract from B. uncinella contained two triterpenoids (oleanolic and ursolic acids) and one flavonoid (pectolinaringenin), whereas the respective EtOAc phase showed to be composed mainly by two phenylpropanoid derivatives (caffeic and ferulic acids). The CH(2)Cl(2) and EtOAc phases as well as their isolated compounds exhibited anti-inflammatory effects against inflammatory reactions induced by phospholipase A2 (from Crotalus durissus terrificus venom) and by carrageenan. Discussion and conclusion: The results suggested that the components obtained from partition phases of EtOH extract of B. uncinella could represent lead molecules for the development of anti-inflammatory agents. Additionally, the results confirmed the use of Baccharis genus in the traditional medicine of South America for the treatment of inflammation and other heath disorders. To date, the present work describes for the first time the anti-inflammatory effects of compounds isolated from B. uncinella.

In vitro schistosomicidal effects of some phloroglucinol derivatives from Dryopteris species against Schistosoma mansoni adult worms

The rhizomes of Dryopteris species have popularly been used as vermifuge in flatworm infections. The aim of this work was to evaluate the in vitro schistosomicidal activity of some phloroglucinol compounds, obtained from the rhizomes of Dryopteris species, against Schistosoma mansoni adult worms. All worm pairs were dead after 24 h of incubation with aspidin 25 to 100 mu M (1), flavaspidic acid 50 and 100 mu M (2), methylene-bis-aspidinol 100 mu M (3), and desaspidin 25 to 100 mu M (4). Worms incubated with 1 (25 to 100 mu M) and 2 (50 to 100 mu M) showed decrease motor activity with tegumental alterations, while 3 (100 mu M) and 4 (10 to 100 mu M) showed decrease motor activity without tegumental alterations. Desaspidinol (5) and filicinic acid (6), at the tested concentrations (10 to 100 mu M), did not show activity against adult worms of S. mansoni. Praziquantel (10 mu M), used as positive control, caused death of the parasites and tegumental alterations without separation of worms. In the groups treated with 100 A mu M of compounds 1-4, the viability of the adult worms was similar to the positive control group, in which the worms were dead. Also, both the egg productions and the development of eggs produced by the adult worms were inhibited by the incubation with compounds 1-4 (10 and 100 mu M) in comparison with the negative control (RPMI 1640 medium). It is suggested that the in vitro schistosomicidal effects of phloroglucinols derivatives 1, 2, 3, and 4 may be related to the inhibition of oxidative phosphorylation pathway in S. mansoni. The present results confirmed the traditional indications of rhizomes from Dryopteris species, which possess phloroglucinol compounds, in the treatment of tapeworm infections.

Effects of Caffeoylquinic Acid Derivatives and C-Flavonoid from Lychnophora ericoides on in vitro Inflammatory Mediator Production

In this study we aimed at evaluating the effect of the major polar constituents of the medicinal plant Lychnophora ericoides on the production of inflammatory mediators produced by LPS-stimulated U-937 cells. The 6,8-di-C-beta-glucosylapigenin (vicenin-2) presented no effect on tumor necrosis factor (TNF)-alpha production, but inhibited, in a dose-dependent manner, the production of prostaglandin (PG) E(2) without altering the expression of cyclooxygenase (COX) -2 protein. 3,5-Dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid, at lower concentrations, had small but significant effects on reducing PG E, levels; at higher doses these compounds stimulated PGE(2) and also TNF-alpha production by the cells. All the caffeoylquinic acid derivatives, in a dose-dependent fashion, were able to inhibit monocyte chemoattractant protein-3 synthesis/release, with 4,5-DCQ being the most potent at the highest tested concentration. These results add important information on the effects of plant natural polyphenols, namely vicenin-2 and caffeoylquinic acid derivatives, on the production of inflammatory mediators by cultured cells.

2-(4,5,6,7-tetrafluorobenzimidazol-2-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, a hydrogen-bonded organic quasi-1D ferromagnet

The title radical (F4BlmNN) is a stable nitronylnitroxide that forms hydrogen-bonded NH center dot center dot center dot ON chains in the solid state. The chains assemble the F4BlmNN molecules to form stacked contacts between the radical groups, in a geometry that is expected to exhibit ferromagnetic (FM) exchange based on spin polarization (SP) models. The experimental magnetic susceptibility of F4BlmNN confirms the expectation, showing 1-D Heisenberg chain FM exchange behavior over 1.8-300 K with an intrachain exchange constant Of J(chain)/k = +22 K. At lower temperatures, ac magnetic susceptibility and variable field heat capacity measurements show that F4BlmNN acts as a quasi-1-D ferromagnet. The dominant ferromagnetic exchange interaction is attributable to overlap between spin orbitals of molecules within the hydrogen-bonded chains, consistent with the SP model expectations. The chains appear to be antiferromagnetically exchange coupled, giving cusps in the ac susceptibility and zero field heat capacity at lower temperatures. The results indicate that the sample orders magnetically at about 0.7 K. The magnetic heat capacity ordering cusp shifts to lower temperatures as external magnetic field increases, consistent with forming a bulk antiferromagnetic phase below a Neel temperature of T-N(0) = 0.72 K, with a critical field of H-c approximate to 1800 Oe. The interchain exchange is estimated to be zJ/k congruent to (-)0.1 K.

On the effective potential in higher-derivatives superfield theories

we study the one-loop quantum corrections for higher-derivative superfield theories, generalizing the approach for calculating the superfield effective potential. In particular, we calculate the effective potential for two versions of higher-derivative chiral superfield models. We point out that the equivalence of the higher-derivative theory for the chiral superfield and the one without higher derivatives but with an extended number of chiral superfields occurs only when the mass term is contained in the general Lagrangian. The presence of divergences can be taken as an indication of that equivalence. (C) 2009 Elsevier B.V. All rights reserved.

Copper(II) and zinc(II) complexes with 2-formylpyridine-derived hydrazones

In the present work 2-formylpyridine-para-chloro-phenyl hydrazone (H2FopCIPh) and 2-formylpyridine-para-nitro-phenyl hydrazone (H2FopNO(2)Ph) were obtained, as well as their copper(II) and zinc(II) complexes [Cu(H2FopClPh)Cl(2)] (1), [Cu(2FopNO(2)Ph)Cl] (2), [Zn(H2FopClPh)Cl(2)] (3) and [Zn(H2FopNO(2)Ph)Cl(2)] (4). Upon re-crystallization in DMSO:acetone conversion of 2 into [Cu(2FopNO(2)Ph)Cl(DMSO)] (2a) and of 4 into [Zn(2FopNO(2)Ph)Cl(DMSO)] (4a) occurred. The crystal structures of 1, 2a, 3 and 4a were determined. (C) 2009 Elsevier Ltd. All rights reserved.

Molecular conformation of the racemic indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide

This paper presents the structural characterization of the indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide, which was unambiguously determined by X-ray diffraction (XRD) to be a racemate (R/S: 50/50) crystallizing in an achiral crystal structure (P2(1)/c, a = 9.3180(1) , b = 7.9070(2) , c = 19.7550(4) , beta = 103.250(1)A degrees, V = 1416.75(5) (3) and Z = 4). The diastereomers are related by the inversion symmetry and linked by H bond forming a dimer. The crystal packing is stabilized by hydrogen bonds, including the classical one responsible for the formation of centrosymmetric dimers, and non-classical ones involving C-H center dot center dot center dot O and C-H center dot center dot center dot pi-aryl interactions. The intra and intermolecular geometry of the title compound is compared to the (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxylic acid one, which also present an achiral crystal structure from racemates (R/S: 50/50). The two indan derivatives crystallize in a very similar unit cell.

Structural studies on zinc(II) complexes with 2-benzoylpyridine-derived hydrazones

2-Benzoylpyridine-phenylhydrazone (H2BzPh), 2-benzoylpyridine-para-chloro-phenylhydrazone (H2BzpClPh), and 2-benzoylpyridine-para-nitro-phenyl (H2BzpNO(2)Ph) hydrazone were obtained and fully characterized, as well as their zinc(II) complexes [Zn(H2BzPh)Cl(2)] (1), [Zn(H2BzClPh)Cl(2)] (2) and [Zn(H2BzpNO(2)Ph)Cl(2)] (3). During the syntheses of complex 1 a second product crystallized, which was characterized as [Zn(2BzPh)(2)] (1a). Upon re-crystallization in 1: 9 DMSO: acetone conversion of 2 into [Zn(H2BzpClPh)Cl2] center dot H(2)O (2a) and of 3 into [Zn(2BzpNO(2)Ph)Cl(DMSO)] (3a) occurred. The crystal structures of 1a, 2a and 3a were determined. In 1a the two nearly perpendicular H2BzPh ligands give rise to a distorted octahedral environment around the metal. The 5-fold coordination around the metal is completed with two chloride ions in 2a and with one chloride and one oxygen atom from DMSO in 3a. (c) 2008 Elsevier B.V. All rights reserved.

Preparation of Achiral and Chiral (E)-Enaminopyran-2,4-diones and Their Phytotoxic Activity

A short and efficient approach to a range of new chiral and achiral functionalized (E)-enaminopyran-2,4-diones starting with commercially available dehydroacetic acid is described. The phytotoxic properties of these (E)-enaminopyran-2,4-diones were evaluated by their ability to interfere with the growth of Sorghum bicolor and Cucumis sativus seedlings. A different sensitivity of the two crops was evident with the (E)-enaminopyran-2,4-diones. The most active compounds were also tested against two weeds, Ipomoea grandifolia and Brachiaria decumbens. To the best of our knowledge, this is the first report describing enaminopyran-2,4-diones as potential plant growth regulators.

Vanadium complexes with 2-pyridineformamide thiosemicarbazones: In vitro studies of insulin-like activity

Reaction of VOCl(2) with 2-pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-methyl (H2Am4Me), N(4)-ethyl (H2Am4Et) and N(4)-phenyl (H2Am4Ph) derivatives in ethanol gave as products [VO(H2Am4DH) Cl(2)] (1), [VO(H2Am4Me) Cl(2)] center dot 1/2HCl (2), [VO(H2Am4Et) Cl(2)] center dot HCl (3) and [VO(2Am4Ph) Cl] (4). Upon the dissolution of 1-4 in water, oxidation immediately occurs with the formation of [VO(2)(2Am4DH)] (5), [VO(2)(2Am4Me)] (6), [VO(2)(2Am4Et)] (7) and [VO(2)(2Am4Ph)] (8). The crystal and molecular structures of 5 and 6 were determined. Complexes 5-8 inhibited glycerol release in a similar way to that observed with insulin but showed a low enhancing effect on glucose uptake by rat adipocytes. (C) 2008 Elsevier B.V. All rights reserved.

Convergent synthesis and cruzain inhibitory activity of novel 2-(N `-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines

To search for new cruzain inhibitors, the synthesis of a series of novel 2-(N`-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines in a convergent manner is presented. The cruzain inhibitory activity of some of these compounds was evaluated and a binding model was proposed. All derivatives tested were active and the most significant inhibitory effect (80% at 100 mu M) and IC(50) value (85 mu M) were obtained from the 2-(N`-4-chloro-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine. Although further structural optimization to improve solubility is necessary, the molecular docking studies suggest that these inhibitors occupy the S2 pocket without irreversible enzyme inactivation, through hydrophobic interactions, thus, indicating a desirable mode of interaction for the design of novel inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

Combined Crystallographic and Solution Molecular Dynamics Study of Allosteric Effects in Ester and Ketone p-tert-Butylcalix[4]arene Derivatives and Their Complexes with Acetonitrile, Cd(II), and Pb(II)

We describe here a procedure to bridge the gap in the field of calixarene physicochemistry between solid-state atomic-resolution structural information and the liquid-state low-resolution thermodynamics and spectroscopic data. We use MD simulations to study the kinetics and energetics involved in the complexation of lower rim calix[4]arene derivatives (L), containing bidentate ester (1) and ketone (2) pendant groups, with acetonitrile molecule (MeCN) and Cd2+ and Pb2+ ions (M2+) in acetonitrile solution. On one hand, we found that the prior inclusion of MeCN into the calix to form a L(MeCN) adduct has only a weak effect in preorganizing the hydrophilic cavity toward metal ion binding. On the other hand, the strong ion-hydrophilic cavity interaction produces a wide open calix which enhances the binding of one MeCN molecule (allosteric effect) to stabilize the whole (M2+)1(MeCN) bifunctional complex. We reach two major conclusions: (i) the MD results for the (M2+)1(MeCN) binding are in close agreement with the ""endo"", fully encapsulated, metal complex found by X-ray diffraction and in vacuo MD calculations, and (ii) the MD structure for the more flexible 2 ligand, however, differs from the also endo solid-state molecule. In fact, it shows strong solvation effects at the calixarene lower bore by competing MeCN molecules that share the metal coordination sphere with the four C=O oxygens of an ""exo"" (M2+)2(MeCN) complex.

Dimethylthallium(III) complexes with picolinic acid and its hydroxyl derivatives

The reaction of dimethylthallium(III) hydroxide with picolinic acid (Hpic), 3-hydroxypicolinic acid (H(2)3hpic) and 6-hydroxypicolinic acid (H(2)6hpic) in an aqueous/methanol mixture afforded the complexes [TlMe(2)(pic)] (1), [TlMe(2)(H3hpic)] (2) and [TlMe(2)(H6hpic)] (3), respectively. Complex 3`, [NaTlMe(2)(6hpic)(2)](n), was obtained as a minor product from a methanolic solution of 3. Compounds 1-3 were characterized by IR and Raman spectroscopy and, in the cases of 1, 2 and Y, by single-crystal X-ray diffraction. Complex 3` is the first example of an H6hpic(-) heterobimetallic compound to be isolated. The (1)H and (13)C NMR spectra of 1 and 2 are also discussed. (c) 2008 Elsevier Ltd. All rights reserved.

Dithiocarbazate complexes with the [M(PPh(3))](2+) (M=Pd or Pt) moiety Synthesis, characterization and anti-Tripanosoma cruzi activity

New neutral Pd(II) and Pt(II) complexes of the type [M(L)(PPh(3))] (M Pd or Pt) were prepared in crystalline form in high-yield synthesis with the S-benzyldithiocarbazates and S-4-nitrobenzyldithiocarbazates derivatives from 2-hydroxyacetophenone, H(2)L(1a) and H(2)L(1b), and benzoylacetone, H(2)L(2a) and H(2)L(2b). The new complexes [Pt(L(1a))(PPh(3))] (1), [Pd(L(1a))(PPh(3))] (2), [Pt(L(1b))(PPh(3))] (3), [Pd(L(1b))(PPh(3))] (4), [Pt(L(2a))(PPh(3))] (5), [Pd(L(2a))(PPh(3))] (6), [Pt(L(2b))(PPh(3))] (7) and [Pd(L(2b))(PPh(3))] (8) were characterized on the basis of elemental analysis, conductivity measurements, UV-visible, IR, electrospray ionization mass spectrometry (ESI-MS), NMR ((1)H and (31)P) and by X-ray diffraction studies. The studies showed that differently from what was observed for the H(2)L(1a) and H(2)L(1b) ligands, H(2)L(2a) and H(2)L(2b) assume cyclic forms as 5-hydroxypyrazolinic. Upon coordination, H2L2a and H2L2b suffer ring-opening reaction, coordinating in the same manner as H(2)L(1a) and H(2)L(1b), deprotonated and in O,N,S-tridentate mode to the (MPPh(3))(2+) moiety. All complexes show a quite similar planar fourfold environment around the M(II) center. Furthermore, these complexes exhibited biological activity on extra and intracellular forms of Trypanosoma cruzi in a time- and concentration-dependent manner with IC(50) values ranging from 7.8 to 18.7 mu M, while the ligand H(2)L(2a) presented a trypanocidal activity on trypomastigote form better than the standard drug benznidazole. (C) 2010 Elsevier Inc. All rights reserved.

Role of cis-cis muconic acid in the catalysis of Pseudomonas putida chlorocatechol 1,2-dioxygenase

Chlorocatechol 1,2-dioxygenase (1,2-CCD) is a non-heme iron protein involved in the intradiol cleavage of aromatic compounds that are recalcitrant to biodegradation. In particular, 1,2-CCD catalyzes the conversion of catechol and its halogenated derivatives to cis-cis muconic acid. In this study we describe a series of experiments concerning the interaction of chlorocatechol 1,2-dioxygenase from Pseudomonas putida (Pp1,2-CCD) with cis-cis muconic acid. We used single-injection ITC to show that the reaction product inhibits enzyme kinetics. DSC and EPR measurements probed whether this was accomplished by a direct binding of the product to the enzyme active site. DSC shows that cis-cis muconic acid affects the thermal unfolding of the protein and allowed us to estimate a binding constant. Furthermore, EPR spectra of the Fe(III) center demonstrate that, upon product binding, a significant decrease in resonance intensity is observed, indicating that cis-cis muconic acid binds directly to the active site. Based on the increasing interest for understanding dioxygenases mechanism of action and, moreover, how to control such process, our data indicate that the product of the reaction does play a relevant role in the catalysis and should therefore be taken into account when one thinks about ways of regulating enzyme activity. (C) 2010 Elsevier B.V. All rights reserved.