Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Tricomas foliares em tomateiro com teores contrastantes do aleloquímico 2-tridecanona

Duas espécies de tomateiro, Lycopersicon esculentum Mill. (Linhagem TOM 556- padrão com baixo teor da metil cetona 2-tridecanona (2-TD) e Lycopersicon hirsutum Dunal var. glabratum Mill. (Linhagem PI 134417- padrão com elevado teor de 2-TD), foram analisadas em conjunto para identificação e quantificação de tricomas foliares. A parte experimental constou da identificação dos tricomas, baseado na presença ou ausência da cabeça secretora na extremidade apical dos tricomas, arranjo e número de células da cabeça, comprimento dos tricomas, e da quantificação do número de tricomas glandulares e não glandulares nos folíolos. O delineamento utilizado para o número de tricomas foi inteiramente casualizado e as médias comparadas pelo teste de Tukey, a 5%. A identificação e quantificação para as espécies foram: a) TOM 556: Tricomas não glandulares do tipo II + III + V (2590 cm-2 de área foliolar); glandular do tipo VI (16 cm-2); glandular do tipo VII (138 cm-2); b) PI 134417: não glandulares do tipo II + III + V (140 cm-2 de área foliolar); glandular do tipo I + IV (843 cm-2); glandular do tipo VI (83 cm-2); glandular do tipo VII (11 cm-2). As maiores concentrações da 2-TD nos folíolos, estão associadas às maiores densidades de tricomas glandulares presentes em ambas espécies.

Frequência de Lettuce big-vein associated virus e Mirafiori lettuce big-vein virus em Plantas de alface no Estado de São Paulo e transmissão através de extrato vegetal e solo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bioactive pyrones and flavonoids from Cryptocarya ashersoniana seedlings

The bioassay directed fractionation of the EtOH extract from leaves of Cryptocarya ashersoniana seedlings led to the isolation of two flavonol glucosides: iso-quercitrin and hyperin, which exhibited free radical scavenging activity towards DPPH (IC50 34.4 muM and 32.7 muM, respectively) and were compared to standard compounds rutin (IC50 27.0 muM) and catechin (IC50 41.4 muM). Investigation of extracts from the seedlings roots and stems afforded one antifungal styrylpyrone: goniothalamine, and two dihydropyrones: 6-propyl-5,6-dihydro-2-pyrone and the new 6-[(4'-ethyl-9'-oxabicyclo[3.3.1]non-6'-en-3'-yl)methyl]-5,6-dihydro-2H-pyran-2-one, which had its structure determined by detailed analysis of MS and NMR data, including 2D experiments.

Kinetics and mechanism of the induced redox reaction of [Ni(cyclam)](2+) promoted by SO5 center dot-

Oxidation of [Ni(cyclam)](2+), cyclam = 1,4,8,11-tetraazacyclotetradecane, accelerated by sulfur dioxide, was studied spectrophotometrically by following the formation of [Ni(cyclam)](3+) under the conditions: [Ni(cyclam)](2+) = 6.0 x 10(-3) M; initial [Ni(cyclam)](3+) = 8.0 x 10(-6) M; [cyclam] = 6.0 x 10(-3) M; [SO2] = (1.0-5.0) x 10(-4) M and 1.0 M perchloric acid in oxygen saturated solutions at 25.0 degrees C and ionic strength = 1.0 M. The oxidation reaction exhibits autocatalytic behavior in which the induction period depends on the initial Ni(III) concentration. A kinetic study of the reduction of Ni(III) by SO2 under anaerobic conditions, and the oxidation of Ni(II), showed that the rate-determining step involves reduction of Ni(III) by SO2 to produce the SO3.- radical, which rapidly reacts with dissolved oxygen to produce SO5.- and rapidly oxidizes Ni(II). The results clearly show a redox cycling process which depends on the balance of SO2 and oxygen concentrations in solution.

Atypical beta-adrenoceptor subtypes mediate relaxations of rabbit corpus cavernosum

This study was performed to characterize the beta-adrenoceptor population in rabbit isolated corpus cavernosum (RbCC) by using nonselective and selective beta-adrenoceptor agonists and antagonists in functional assays. Metaproterenol, ritodrine, fenoterol, and 8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(rho-methoxy-phenyl)1-methylethyl] amino] ethyl] carbostyril (TA 2005) (3-100 nmol each) dose dependently relaxed the RbCC preparations. These relaxations were markedly reduced by N-omega-nitro-L-arginine methyl ester (L-NAME; 10 muM) and 1H-[1,2,4]-oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ) (10 muM), whereas the adenylyl cyclase inhibitor SQ 22,536 [9-(2-tetrahydrofuryl)adenine] (10 muM) had no effect. In contrast, neither L-NAME nor ODQ affected the isoproterenol-induced RbCC relaxations, but SQ 22,536 abolished this response. Sildenafil (1 muM) significantly potentiated the relaxations induced by beta(2)-agonists without affecting the isoproterenol-evoked relaxations. Rolipram (10 muM) enhanced the relaxations elicited by isoproterenol but had no effect on those induced by the selective beta(2) agonists. Propranolol and (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanolhydrochloride (ICI 118,551) determined a rightward shift in the concentration-response curves to isoproterenol in a noncompetitive manner with a reduction of maximum response at the highest antagonist concentration, with the slope values significantly different from unity. Propranolol and ICI 118,551 had no effect on the relaxations elicited by fenoterol, TA 2005, metaproterenol, and ritodrine. Atenolol and 1-[2-((3-carbamoyl-4-hydroxy)phenoxy) ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]2-propanol methanesulfonate (CGP 20712A) (0.1-10 muM) failed to affect the relaxations induced by all tested beta-adrenoceptor agonists. Our study revealed the existence of two atypical beta-adrenoceptors in the rabbit erectile tissue. Isoproterenol relaxes the rabbit cavernosal tissue by activating atypical beta-adrenoceptors coupled to adenylyl cyclase pathway, whereas the selective beta2-adrenoceptor agonists relax the RbCC tissue through another atypical beta-adrenoceptor subtype coupled to nitric oxide release from the sinusoidal endothelium.

Influence of the cultivation system in the aroma of the volatile compounds and total antioxidant activity of passion fruit

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Planejamento, síntese e avaliação farmacológica de compostos híbridos potencialmente ativos para o tratamento da anemia falciforme

Sickle cell disease (SCD) is a hereditary hemolytic anemia caused by the inheritance of one S hemoglobin gene from each ancestor. Patients with SCD present increased circulating levels of cytokines, including TNF-alpha (TNF-α). Hydroxyurea (HU) is the available therapeutically strategy for treatment; it acts as a source of nitric oxide and benefits patients by increasing the levels of fetal hemoglobin (HbF). Thus, within one research line that aims at finding new drugs, a series of compounds with TNF-α inhibition and nitric oxide donation properties have been synthesized in order to explore possible synergism of actions beneficial in the treatment of the disease. Six compounds were synthesized: five derivatives of organic nitrates and one of sulfonamide. The compounds, (1,3-dioxo-1,3-dihydro-2Hisoindol-2-yl) methyl nitrate (compound I); (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethyl nitrate (compound II); 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (compound III);4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxybenzenesulfonamide (compound IV); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (compound V) and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) phenyl]ethyl nitrate (compound VI), were synthesized using linear synthetic methodology, with excellent overall yields. All compounds showed anti-inflammatory and analgesic effects with a reduction in 43%-65% of ear edema in mice and a reduction of 25%-42% of writhing induced by acetic acid. All compounds showed comparable reductions in the leukocyte infiltration capacity and ability to generate nitric oxide. The aryl compounds (III, IV and V) presented less mutagenic activity compared to compounds I, II and VI according to the salmonella mutagenicity assay (Ames test). Compounds IV and VI showed activity in K562 culture cells, with increases in gamma globin gene expression to levels higher than with hydroxyurea suggesting a potential to increase fetal hemoglobin. This data set characterizes new potentially useful drug candidates for the treatment of symptoms of sickle cell anemia.

Estudo da afinidade das proteínas rTgMIC1 e rTgMIC4 da Toxoplasma gondii com fetuína e asialofetuína utilizando técnica piezelétrica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Planejamento, síntese e avaliação farmacológica de compostos híbridos potencialmente ativos para o tratamento da anemia falciforme

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Structural characterization of an etheno-2 '-deoxyguanosine adduct modified by tetrahydrofuran

The reaction of 2'-deoxyguanosine with the alpha,beta-unsaturated aldehydes trans-2-octenal, trans-2-nonenal, trans-2-decenal, trans,trans-2,4-nonadienal, and trans,trans-2,4-decadienal in THF gives rise to three novel adducts: 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-[3-hydroxy-1-(3(2'-deoxy-beta-D-erythro-pentafuranosyl)-3,5-dihydro-imidazo[1,2-alpha]purin-9-one-7-yl)-propyl] -3,5-dihydro-imidazo[1,2-alpha]purin-9-one (M) and 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-(tetrahydrofuran-2-yl)-3,5-dihydro-imidazo[1,2-alpha]purin-9-one (A8 and A9), which are not observed in the absence of THF. These adducts were isolated from in vitro reactions by reversed-phase HPLC and fully characterized on the basis of spectroscopic measurements. Adduct A7 consists of two 1,N-2-etheno-2'-deoxyguanosine (1,N-2-epsilondGuo) residues linked to a hydroxy-carbon side chain; adducts A8 and A9 are interconvertible 1,N-2-epsilondGuo derivatives bearing a THF moiety. The proposed reaction mechanism involves the electrophilic attack on 1,N-2-epsilondGuo by the carbonyl of 4-hydroxy-butanal, generated via ring opening of alpha-hydroxy-THF (THF-OH), yielding adducts A8 and A9. A further combination of these adducts with another 1,N-2-epsilondGuo produces the double adduct A7. These findings demonstrate that reactions of unsaturated aldehydes in the presence of THF produce novel condensation 1,N-2-epsilondGuo-THF adducts. Further studies would indicate the relevance of these adducts in THF toxicity.

Antiproliferative activity of cardenolide glycosides from Asclepias subulata

Asclepias subulata Decne. is a shrub occurring in Sonora-Arizona desert (Mexico-USA). The ethnic groups, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. To isolate the compounds responsible for antiproliferative activity of the methanol extract of A. subulata. A bioguided fractionation of methanol extract of A. subulata was performed using MTT assay to measure the antiproliferative activity of different compounds on three human cancer cell lines (A549, LS 180 and PC-3), one murine cancer cell line (RAW 264.7) and one human normal cell line (ARPE-19). The methanol extract was partitioned with hexane, ethyl acetate and ethanol. The active fractions, ethanol and residual, were fractioned by silica-column chromatography and active sub-fractions were separated using HPLC. The chemical structures of isolated compounds were elucidated with different chemical and spectroscopic methods. A new cardenolide glycoside, 12, 16-dihydroxycalotropin, and three known, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, were isolated of active sub-fractions. All isolated compounds showed a strong antiproliferative activity in human cancer cells. Calotropin was the more active with IC50 values of 0.0013, 0.06 and 0.41 µM on A549, LS 180 and PC-3 cell lines, respectively; while 12, 16-dihydroxycalotropin reached values of 2.48, 5.62 and 11.70 µM, on the same cells; corotoxigenin 3-O-glucopyranoside had IC50 of 2.64, 3.15 and 6.62 µM and desglucouzarin showed values of 0.90, 6.57 and 6.62, µM. Doxorubicin, positive control, showed IC50 values of 1.78, 6.99 and 3.18 µM, respectively. The isolated compounds had a weak effect on murine cancer cells and human normal cells, exhibiting selectivity to human cancer cells. In this study, we found that 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin are responsible of antiproliferative properties of A. subulata, and that these compounds are highly selective to human cancer cells. Further studies are needed in order to establish the action mechanisms of the isolated compounds.

Semiparametric modeling of the spatial distribution of occupational accident risk in the casual labor market, Piracicaba, southeast Brazil

The objective of this study was to estimate the spatial distribution of work accident risk in the informal work market in the urban zone of an industrialized city in southeast Brazil and to examine concomitant effects of age, gender, and type of occupation after controlling for spatial risk variation. The basic methodology adopted was that of a population-based case-control study with particular interest focused on the spatial location of work. Cases were all casual workers in the city suffering work accidents during a one-year period; controls were selected from the source population of casual laborers by systematic random sampling of urban homes. The spatial distribution of work accidents was estimated via a semiparametric generalized additive model with a nonparametric bidimensional spline of the geographical coordinates of cases and controls as the nonlinear spatial component, and including age, gender, and occupation as linear predictive variables in the parametric component. We analyzed 1,918 cases and 2,245 controls between 1/11/2003 and 31/10/2004 in Piracicaba, Brazil. Areas of significantly high and low accident risk were identified in relation to mean risk in the study region (p < 0.01). Work accident risk for informal workers varied significantly in the study area. Significant age, gender, and occupational group effects on accident risk were identified after correcting for this spatial variation. A good understanding of high-risk groups and high-risk regions underpins the formulation of hypotheses concerning accident causality and the development of effective public accident prevention policies.

Sediment toxicity assessment of Guanabara Bay, Rio de Janeiro, Brazil.

Guanabara Bay (GB) comprises of estuarine and marine environments of high ecological and socio-economic relevance, together with port, industrial and urban areas. The anthropogenic activities produce environmental impacts, including the aquatic pollution. The sediment quality assessment is important to evaluate the effects of contamination, once sediments are a repository for most of the contaminants. In this Study, the quality of sediments from GB was evaluated, in rainy and dry periods, throughout the employment of acute toxicity tests with the amphipod Tiburonella viscana, and chronic bioassays with embryos of the sea-urchin Lytechinus variegatus. In the dry period, acute toxicity was found in the sediments from stations 1, 2 3 (NW) and 7 (near Guapimirim Environmental Protection Area). The bioassays with liquid phases showed effects, but were strongly influenced by the unionized ammonia levels, which were high in this period. In the rainy period, acute toxicity was found in sediments samples from stations 1, 2, 3, 6, 8, 10, 11, 12 and 15. Chronic toxicity could be clearly detected, as ammonia concentrations tended to be low in the most part of the samples. The results showed that the sediment toxicity is influenced by precipitation rates, which increase the input of contaminants to the Bay, and also allowed subdividing GB in three main zones: northwest (stations 1, 2, 3, 5), northeast (stations 6, 7, 8, 9) and centre-south (stations 10, 11, 12, 13, 14, 15). Results also showed that the quality of GB sediments is poor, and that toxicity tests could determine the combined effects of pollutants.