Ésteres triterpênicos de Himatanthus sucuuba (Spruce) Woodson

Bioactivity-guided fractionation from hexane extract of Himatanthus sucuuba barks utilizing Cladosporium sphaerospermum led to the isolation of iridoids plumericin and isoplumericin, which showed higher inhibition against C. sphaerospermum than the antibiotic nistatin. Besides bioactive iridoids were isolated the inactive triterpenes lupeol cinnamate, alpha-amyrin cinnamate and lupeol acetate.

Flavonóides glicosilados das folhas e flores de Bauhinia forficata (Leguminosae)

From the leaves of Bauhinia forficata kaempferol and four flavonoid glycosides, 3,7-di-O-alpha-L-rhamnopyranosylkaempferol, 3,7-di-O-alpha-L-rhamnopyranosylquercetin, 3-O-[alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranosyl]-7-O-alpha-L-rhamnopyranosylkaempferol and 3-O-[alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranosyl]-7-O-alpha-L-rhamnopyranosylquercetin were obtained. From the flowers only the flavonoid 7-O-alpha-L-rhamnopyranosylkaempferol was isolated. The structures were established by chemical and spectroscopic methods.

Flavonóide e triterpenos de Stigmaphyllom paralias

Stigmaphyllom paralias is a herb belonging to the family Malpighiaceae that occurs in sand soil of brazilian " restinga". This is the first report regarding phytochemical study with this species. The hexane extract of the aerial parts of plant afforded the triterpenes friedelin, lupenone, 3-oxo-alpha-amirin and 3-oxo-beta-amirin, the mixture of alpha-amirinyl palmitate and stearate, lupeol and 3,4-seco-friedelan-3-oic acid. The AcOEt extract yielded the flavonoid luteolin-7-rutinoside. All compounds were characterized by analysis of spectrometric data and the fatty acids esterified with alpha-amirine were identified by GC/MS of methyl derivatives of transesterified products . This is the first natural occurence of 3,4-seco-friedelan-3-oic acid and the 13C NMR spectral data were inequivocally assigned by two-dimensional techniques. This work also permitted to correct the 13C NMR resonances attributed to methyl groups C-26 and C-27 of fridelin.

Síntese de novos herbicidas derivados do 1,2alfa,4alfa,5-tetrametil-8-oxabiciclo[3.2.1]oct-6-en-3-ona

In this paper we report the synthesis of biologically active compounds through a [3+4] cycloaddition reaction to produce the main frame structure, followed by several conventional transformations. The 1,2alpha,4alpha,5-tetramethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (11) obtained from a [3+4] cycloaddition reaction was converted into 1,2alpha,4alpha,5-tetramethyl-6,7-exo-isopropylidenedioxi-8 -oxabicyclo[3.2.1]octan-3-one (13) in 46% yield. This was further converted into the alcohols 1,2alpha,4alpha,5-tetramethyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (14), 1,2alpha,4alpha,5-tetramethyl-6,7-exo-isopropylidenedioxi-8 -oxabicyclo[3.2.1]octan-3beta-ol (15), 1,2alpha,4alpha,5-tetramethyl-3-butyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (17), 1,2alpha,4alpha,5-tetramethyl-3-hexyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (18) and 1,2alpha,4alpha,5-tetramethyl-3-decyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (19). Dehydration of 17, 18 and 19 with thionyl chloride in pyridine resulted in the alkenes 20, 21 and 22 in ca. 82% - 89% yields from starting alcohols. The herbicidal activity of the compounds synthesized was evaluated at a concentration of 100 µg g-1. The most active compound was 21 causing 42,7% inhibition against Cucumis sativus L.

Constituintes químicos da raiz e do talo da folha do açaí (Euterpe precatoria Mart., Arecaceae)

Phytochemical investigation of the hexane, ethyl acetate and methanolic extracts of roots and leaf stalks of Euterpe precatoria Mart. ("açaí"), afforded stigmast-4-en-6beta-ol-3-one (3); p-hydroxy benzoic acid (4); 3beta-O-D-glucopyranosyl-sitosterol (5); beta-sitosterol palmitate (6); mixtures of beta-sitosterol and stigmasterol (1 and 2), alpha-, beta-amirin and lupeol (7, 8 and 9), friedelin-3-one and 28-hydroxy-friedelin-3-one (10 and 11) and alpha-, beta-D-glucose (12, 13). Except for 1, 2 and 4, the other isolated constituents are described in the genus for the first time. Compounds 3 and 5 gave good results in the brine shrimp bioassay, which detects compounds with potential uses as antitumor agents, pesticides, etc..

Reações de carbociclização radicalar de orto-iodoaliloxibenzoatos derivados de d-glicose e d-galactose e comparação com as reações de seus análogos benzamidas

Two ortho-iodoallyloxybenzoates, methyl 4-O-allyl-2,3-di-O-benzyl-6-O-(2-iodobenzoyl)- alpha-D-glucopyranoside (3) and methyl 4-O-allyl-2,3-di-O-benzyl-6-O-(2-iodobenzoyl)- alpha-D-galactopyranoside (4) were synthesized in seven conventional steps from methyl alpha-D-glucopyranoside and methyl alpha-D-galactopyranoside, respectively. Bu3SnH-mediated aryl radical cyclization of 3 provided exclusively the hydrogenolysis product 12. The reaction of 4 gave the reduced uncyclized product 13 and only traces of 4A, resulting from 11-endo aryl radical cyclization. In previous papers we described that in similar Bu3SnH-mediated radical reaction of ortho-iodoallyloxybenzamides, analogs of 3 and 4, we obtained macrolactams resulting from 11-endo cyclization. An hypothesis to explain the differences is presented. It was assumed that in the aryl radical formed from iodobenzamides there is a suitable conformation to cyclization, which is stabilized by an intramolecular hydrogen bond.

Estresse oxidativo: relação entre geração de espécies reativas e defesa do organismo

This work describes the mechanism of action of some reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the oxidative stress of the human body, and their consequences on damage to DNA, RNA, proteins and lipids. It also illustrates the defense system of our organism against these ROS and RNS species. The action of nonenzymatic protection systems is reported, with emphasis on micromolecules like Q10 coenzyme, vitamin C, alpha-tocopherol, carotenoids and flavonoids. The importance of flavonoids is also emphasized, and their body protection mechanism is detailed.

Preparative separation of flavonoids from the medicinal plant Davilla elliptica St. Hill. by high-speed counter-current chromatography

High-speed counter-current chromatography (HSCCC) is a major tool for the fast separation of natural products from plants. It was used for the preparative isolation of the flavonoid monoglucosides present in the aerial parts of the Davilla elliptica St. Hill. (Dilleniaceae). This species is used in Brazilian folk medicine for the treatment of gastric disorders. The optimum solvent system used was composed of a mixture of ethyl acetate-n-propanol-water (140:8:80, v/v/v) and led to a successful separation of quercetin-3-O-alpha-L-rhamnopyranoside and myricetin-3-O-alpha-L-rhamnopyranoside in approximately 3.0 hours with purity higher than 95%. Identification was performed by ¹H NMR, 13C NMR and HPLC-UV-DAD analyses.

Métodos de obtenção, reatividade e importância biológica de 4-tiazolidinonas

Molecules containing the 4-thiazolidinone ring are known to possess a wide range of biological properties including antimicrobial and anti-inflammatory activities among others. These compounds can be synthesized by cyclization reactions involving alpha-haloacetic acid or alpha-mercaptoacetic acid and employed in several chemoselective reactions. Comprehensive reviews have been written on 4-thiazolidinones in 1961 by Brown and in 1980 by Singh et al. In the recent literature, some new synthesis methods for 4-thiazolidinone derivatives and several reactions have been reported. These advances warrant to review the chemical and biological properties of compounds with this important heterocycle employed in synthetic organic chemistry and medicinal chemistry.

Calcium handling by vascular myocytes in hypertension

Calcium ions (Ca2+) trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1) the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2) Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3) intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension

Antinociceptive effect of intrathecal neostigmine evaluated in rats by two different pain models

The analgesic efficacy of cholinergic agonists and anticholinesterase agents has been widely recognized. The analgesic effect obtained by activating cholinergic mechanisms, however, seems to depend on the experimental pain model utilized for its evaluation. The antinociceptive effect of intraspinal neostigmine was examined in rats submitted concurrently to the tail flick and formalin tests. Neostigmine (8.25 and 16.5 nmol) produced a dose-dependent antinociceptive effect in the tail flick test (a model of phasic pain) and reduced the first phase (phasic pain) of the animal response to formalin also in a dose-dependent manner. The second phase (tonic pain) of the response to formalin, however, was slightly reduced after a longer period of time only by the higher dose of the anticholinesterase. The effect of neostigmine was not significantly different when the drug was injected into rats submitted exclusively to the tail flick test. The second phase of the animal response to formalin was slightly reduced by neostigmine (8.25 nmol) and strongly inhibited by the higher dose of the anticholinesterase when injection was made after the first phase. We conclude that phasic and tonic pain can both be controlled by high doses of neostigmine. In addition, we show that inhibition by a lower dose of neostigmine of the formalin-induced phasic pain did not prevent the subsequent occurrence of tonic pain produced by the irritant

Molecular biology of the kallikrein-kinin system: from structure to function

The participation of the kallikrein-kinin system, comprising the serine proteases kallikreins, the protein substrates kininogens and the effective peptides kinins, in some pathological processes like hypertension and cardiovascular diseases is still a matter of controversy. The use of different experimental set-ups in concert with the development of potent and specific inhibitors and antagonists for the system has highlighted its importance but the results still lack conclusivity. Over the last few years, transgenic and gene-targeting technologies associated with molecular biology tools have provided specific information about the elusive role of the kallikrein-kinin system in the control of blood pressure and electrolyte homeostasis. cDNA and genomic sequences for kinin receptors B2 and B1 from different species were isolated and shown to encode G-protein-coupled receptors and the structure and pharmacology of the receptors were characterized. Transgenic animals expressing an overactive kallikrein-kinin system were established to study the cardiovascular effects of these alterations and the results of these investigations further corroborate the importance of this system in the maintenance of normal blood pressure. Knockout animals for B2 and B1 receptors are available and their analysis also points to the role of these receptors in cardiovascular regulation and inflammatory processes. In this paper the most recent and relevant genetic animal models developed for the study of the kallikrein-kinin system are reviewed, and the advances they brought to the understanding of the biological role of this system are discussed.

Role of sensory nervous system vasoactive peptides in hypertension

The goal of the present research was to elucidate the roles and mechanisms by which the sensory nervous system, through the actions of potent vasodilator neuropeptides, regulates cardiovascular function in both the normal state and in the pathophysiology of hypertension. The animal models of acquired hypertension studied were deoxycorticosterone-salt (DOC-salt), subtotal nephrectomy-salt (SN-salt), and Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertension during pregnancy in rats. The genetic model was the spontaneously hypertensive rat (SHR). Calcitonin gene-related peptide (CGRP) and substance P (SP) are potent vasodilating neuropeptides. In the acquired models of hypertension, CGRP and SP play compensatory roles to buffer the blood pressure (BP) increase. Their synthesis and release are increased in the DOC-salt model but not in the SN-salt model. This suggests that the mechanism by which both models lower BP in SN-salt rats is by increased vascular sensitivity. CGRP functions in a similar manner in the L-NAME model. In the SHR, synthesis of CGRP and SP is decreased. This could contribute to the BP elevation in this model. The CGRP gene knockout mouse has increased baseline mean arterial pressure. The long-term synthesis and release of CGRP is increased by nerve growth factor, bradykinin, and prostaglandins and is decreased by alpha2-adrenoreceptor agonists and glucocorticoids. In several animal models, sensory nervous system vasoactive peptides play a role in chronic BP elevation. In the acquired models, they play a compensatory role. In the genetic model, their decreased levels may contribute to the elevated BP. The roles of CGRP and SP in human hypertension are yet to be clarified.

Validation of the Beck Depression Inventory for a Portuguese-speaking Chinese community in Brazil

The objective of the present study was to investigate the psychometric properties and cross-cultural validity of the Beck Depression Inventory (BDI) among ethnic Chinese living in the city of São Paulo, Brazil. The study was conducted on 208 community individuals. Reliability and discriminant analysis were used to test the psychometric properties and validity of the BDI. Principal component analysis was performed to assess the BDI's factor structure for the total sample and by gender. The mean BDI score was lower (6.74, SD = 5.98) than observed in Western counterparts and showed no gender difference, good internal consistency (Cronbach's alpha 0.82), and high discrimination of depressive symptoms (75-100%). Factor analysis extracted two factors for the total sample and each gender: cognitive-affective dimension and somatic dimension. We conclude that depressive symptoms can be reliably assessed by the BDI in the Brazilian Chinese population, with a validity comparable to that for international studies. Indeed, cultural and measurement biases might have influenced the response of Chinese subjects.

High mobility group box 1 as a mediator of endotoxin administration after hemorrhagic shock-primed lung injury

High mobility group box 1 (HMGB1) was discovered as a novel late-acting cytokine that contributes to acute lung injury (ALI). However, the contribution of HMGB1 to two-hit-induced ALI has not been investigated. To examine the participation of HMGB1 in the pathogenesis of ALI caused by the two-hit hypothesis, endotoxin was injected intratracheally in a hemorrhagic shock-primed ALI mouse model. Concentrations of HMGB1 in the lung of the shock group were markedly increased at 16 h (1.63 ± 0.05, compared to the control group: 1.02 ± 0.03; P < 0.05), with the highest concentration being observed at 24 h. In the sham/lipopolysaccharide group, lung HMGB1 concentrations were found to be markedly increased at 24 h (1.98 ± 0.08, compared to the control group: 1.07 ± 0.03; P < 0.05). Administration of lipopolysaccharide to the hemorrhagic shock group resulted in a notable HMGB1 increase by 4 h, with a further increase by 16 h. Intratracheal lipopolysaccharide injection after hemorrhagic shock resulted in the highest lung leak at 16 h (2.68 ± 0.08, compared to the control group: 1.05 ± 0.04; P < 0.05). Compared to the hemorrhagic shock/lipopolysaccharide mice, blockade of HMGB1 at the same time as lipopolysaccharide injection prevented significantly pulmonary tumor necrosis factor-alpha, interleukin-1beta and myeloperoxidase. Lung leak was also markedly reduced at 16 h; blockade of HMGB1 24 h after lipopolysaccharide injection failed to alter lung leak or myeloperoxidase at 48 h. Our observations suggest that HMGB1 plays a key role as a late mediator when lipopolysaccharide is injected after hemorrhagic shock-primed ALI and the kinetics of its release differs from that of one-hit ALI. The therapeutic window to suppress HMGB1 activity should not be delayed to 24 h after the disease onset.