A new phenylpropanoid derivative, named euploic acid (1), was isolated from Euploca procumbens (Mill.) Diane & Hilger, Boraginaceae, along with lithospermic acid B (2), lithospermic acid (3), 9’’-methyl lithospermate (4), and luteolin-7-O-glucoside (5). Compound structures were determined by mass spectrometry (MS), nuclear magnetic resonance (NMR) analysis and comparison with published data. Absolute configuration of 1 was established via electronic circular dichroism (ECD). Anti-inflammatory potential of euploic acid (1) was assessed by measuring its inhibition of cytokine and nitric oxide production in stimulated J774 macrophages. Compound 1 significantly reduced pro-inflammatory mediator production and release by stimulated macrophages at non-cytotoxic concentrations, comparable to the efficacy of dexamethasone. Our findings demonstrate the potential of euploic acid (1) as an effective anti-inflammatory agent. This study contributes to the structural elucidation of a new phenylpropanoid derivative and highlights its promising anti-inflammatory activity in the treatment of inflammatory disorders. 1, , Mill. Mill (Mill. Hilger Boraginaceae 2, 2 (2) 3, 3 (3) 9methyl methyl 9 4, 4 (4) luteolin7Oglucoside luteolinOglucoside luteolin 7 O glucoside 5. 5 . (5) MS, MS (MS) NMR (NMR data ECD. ECD (ECD) Antiinflammatory Anti (1 J J77 proinflammatory pro noncytotoxic non cytotoxic concentrations dexamethasone antiinflammatory anti agent disorders (Mill (2 (3 (4 Oglucoside (5 (MS (ECD ( J7

Chagas disease, caused by the parasite Trypanosoma cruzi, occurs most commonly in Latin America. As the treatment is highly toxic and ineffective in the chronic phase of the disease, alternative treatments are needed. Through quantitative structure-activity relationship modeling (QSAR) analysis using ligand-based and structure-based virtual screening methods, we predicted the trypanocidal potential of 47 neolignans against three targets, the enzymes cruzain, trypanothione reductase, and sterol 14-alpha demethylase. A combined analysis allowed for the selection of potent inhibitors against Trypanosoma cruzi. Of these compounds, two were isolated and shown to inhibit the growth of epimastigotes at concentrations of 9.64 and 8.72 µM, and trypomastigote forms at 4.88 and 2.73 µM. Therefore, the compounds (2R, 3R)-2,3-dihydro-2 (4 methoxyphenyl)-3-methyl-5-(E)-propenylbenzofuran (46) and ottomentosa (47) may be a good option of growth inhibitors for the parasite stages and warrant additional study. disease cruzi America needed structureactivity structure activity QSAR (QSAR ligandbased ligand based structurebased methods 4 targets cruzain reductase 14alpha alpha 14 demethylase 964 9 64 9.6 872 8 72 8.7 µM 488 88 4.8 273 2 73 2.7 Therefore 2R, 2R R (2R 3R2,3dihydro2 3R23dihydro2 Rdihydro 3R 2,3 dihydro 3 3R)-2,3-dihydro- ( methoxyphenyl3methyl5Epropenylbenzofuran methoxyphenylmethylEpropenylbenzofuran methoxyphenyl methyl 5 E propenylbenzofuran 46 (46 (47 study 1 96 6 9. 87 7 8. 48 4. 27 2. 3R2 3dihydro2 3R2,3dihydro 3R23dihydro 23 2, 3R)-2,3-dihydro Epropenylbenzofuran 3dihydro

The objective of this work was to carry out a bibliographic survey of secondary metabolites isolated from the Velloziaceae family, creating a bank of compounds. After the bank was created, four prediction models for potentially active compounds against pathogenic microorganisms (Candida albicans, Escherichia coli, Pseudomonas aeruginosa and Salmonella sp.) were obtained trying to identify which metabolites would be more active against the strains. Four sets of compounds with known activity for microorganisms were selected for the construction of predictive models from the CHEMBL database. Another bank with 163 unique molecules isolated from the Velloziaceae family was built. The Volsurf+ v.1.0.7 software obtained the molecular descriptors and Knime 3.5 generated the in silico model. The performances of the internal and external tests were also analyzed. The study contributed through the virtual screening of a bank of metabolites to select several compounds with potential antimicrobial activity, highlighting the biflavonoid amentoflavone which showed potential activity against the four strains.

A chemical investigation of Anaxagorea dolichocarpa Sprague & Sandwith, a member of Annonaceae family, was carried out. The ethanolic extract from the roots of this plant led, by chromatography tecniches, to isolation of the new azaphenanthrene alkaloids dolichocarpine (1) and 9-methoxyeupolauramine (2), besides the known alkaloids eupolauramine (3), 3-methoxyeupolauridine (4), eupolauramine (5) and 4-methylsampangine (6). The structures of isolated compounds were established by 1D and 2D NMR, HRESIMS, tandem MSn and IR data. The cytotoxicity of compounds 1 - 5 was evaluated against HCT-116 (human colorectal carcinoma) and L929 (murine fibroblast) cell lines.

RESUMO O objetivo do estudo foi realizar a revisão histológica de casos de meningiomas grau I com necrose espontânea, grau I sem necrose e grau II para avaliar os fatores histológicos e imunohistoquímicos de prognóstico dos pacientes, correlacionando informações no âmbito clínico-patológico com o seguimento clínico dos pacientes. Foi realizada revisão de 47 casos do Departamento de Patologia da UNIFESP e as amostras foram submetidas a exame imunohistoquímico com os marcadores proteína p53, fator de proliferação celular Ki-67 e receptor de progesterona. Verificou-se maior expressão na progressão dos diversos graus de agressividade para p53 e Ki-67 e maior frequência de receptores de progesterona nos menores graus. O grupo dos meningiomas grau I com necrose espontânea apresentou índices histológicos e imuno-histoquímicos que se aproximam dos meningiomas grau II. Isto sugere um pior prognóstico dos meningiomas grau I com necrose.

ABSTRACT The study reviewed the histology of cases of grade I meningiomas with spontaneous necrosis, grade I without necrosis and grade II meningiomas, to evaluate the histological and immunohistochemical factors of the patients’ prognosis, while correlating the clinicopathological features with the clinical follow-up of the patients. A review of 47 cases from the Department of Pathology of UNIFESP was performed and the samples were submitted to immunohistochemical examination with the p53 protein, Ki-67 cell proliferation factor and progesterone receptor markers. A greater expression was found in the progression of several degrees of aggressiveness for p53 and Ki-67, and a higher frequency of progesterone receptors in the lower degrees. The group of grade I meningiomas with spontaneous necrosis showed histological and immunohistochemical indexes that approximate those of the grade II meningioma. This suggests a worse prognosis for grade I meningiomas with necrosis.

The secondary metabolites of the aerial parts of Phyllanthus acuminatus Vahl (Phyllanthaceae) and the biological activity of one of them were characterized in this study. This chemical investigation led to isolation of two lignans, luclaricin (1), a new arylnaphtalene-typelignan, and justicidin B (2). The structures of isolated compounds were determined based on 1D and 2D-NMR, HRESIMS and IR. The cytotoxic activity of justicidin B was assessed against tumor cell lines (MCF-7, U251, NCI-ADR/RES, NCI-H460, OVCAR-3, HT29 and K562) and a non-tumor cell line (HaCat) using sulforhodamine B assay. Justicidin B showed strong cytotoxic activity against the tumor cell lines HT29, K562 and U251 with GI50 values of 2.28, 3.29 and 5.76 mol L-1, respectively.

ABSTRACT The secondary metabolites of the aerial parts of Zornia brasiliensis Vogel, Fabaceae, and the biological activity of one of these secondary metabolites were characterized in this study. A phytochemical investigation was performed using chromatographic techniques including analytical and preparative reverse-phase HPLC column sequences, which resulted in the isolation of fourteen compounds: one previously undescribed C-glycosylated dihydrochalcone (zornioside), one cyclitol (D-pinitol), one glycosylated megastigmane (roseoside) and eleven phenolic compounds: 7-methoxyflavanone, 7,4'-dimethoxyisoflavone, medicarpin, 2'-4'-dihydroxychalcone, onionin, isoorientin-3'-O-methyl ether, isovitexin, glycosylated (Z)-O-coumaric acid, glycosylated (E)-O-coumaric acid, dihydromelilotoside, and isoorientin. The structures of the isolated compounds were determined based on 1D and 2D-NMR, HRESIMS, IR and CD spectroscopic analyses. The cytotoxic activity of zornoside was assessed against tumor cell lines (MCF-7, HCC1954, T-47D, 4T1, HL60), and a non-tumor cell line (RAW264.7) using MTT assay. The compound zornioside was selectively cytotoxic for HL60 leukemia cells (IC50: 37.26 µM).

ABSTRACT The essential oil from Croton polyandrus Spreng., Euphorbiaceae, leaves was tested for the toxicity and antitumor activity. The concentration producing 50% hemolysis was 141 µg/ml on mice erythrocytes. In the acute toxicological study, the estimated LD50 was 447.18 mg/kg. The essential oil did not induce increase in number of micronucleated erythrocytes, suggesting low genotoxicity. Essential oil (100 or 150 mg/kg) showed significant antitumor activity in Ehrlich ascitic carcinoma model. We observed that essential oil induces cell-cycle arrest at the G0/G1 phase, and increases the sub-G1 peak, which represents a marker of cell death by apoptosis. Survival also increased for the treated animals. The toxicological analyses revealed reduction in body weight, increased aspartate aminotransferase and alanine aminotransferase activity, hematological changes, and a thymus index reduction. These data suggest gastrointestinal and liver toxicity, anemia, leukopenia/lymphocytopenia, and immunosuppressive effects. Histopathological analysis revealed the weak hepatotoxicity of essential oil. In summary, essential oil of C. polyandrus displays in vivo antitumor activity and moderate toxicity.

Combretum duarteanum Cambess, Combretaceae, is a plant widely distributed in Northeastern Brazil and, in folk medicine, stems and leaves are used for pain treatment. We investigated the antinociceptive effects of the hexanic extract of leaves from C. duarteanum and of friedelin, its main compound, in formalin-, glutamate- and capsaicin- induced orofacial nociception models. In order to isolate friedelin from the hexanic extract, flash chromatography technique was used. Male mice (n = 8/group) were pretreated with hexanic extract, friedelin, morphine or vehicle, before the injection of algogen agents into the right upper lip (perinasal area). The test of formalin-induced orofacial nociception showed that hexanic extract and friedelin significantly reduced nociception (p < 0.001) in both phases of testing. In the glutamate and capsaicin-induced orofacial nociception tests, pre-treatment with hexanic extract produced a significant reduction of orofacial nociception (p < 0.001) at all doses tested.The results suggest the hexanic extract and friedelin possess antinociceptive effects in models of orofacial nociception in rodents.

A investigação fitoquímica das raízes de Krameria tomentosa A. St. -Hil. levou ao isolamento de cinco neolignanas, duas delas com estruturas inéditas [1,1'-(E)-propenil4-metóxi-3,4'-oxineolignana (ottomentosa) e ácido 2-(2'-hidróxi-4',6'-dimetoxifenil) benzofurano-5-carboxílico (sobralina)], além de três compostos conhecidos [eupomatenoide 6, di-hidrocarinatidina e 2-(2',4'-di-hidroxifenil)-5-(E)-propenilbenzofurano]. A caracterização estrutural dos compostos isolados foi estabelecida com base na espectroscopia no infravermelho, espectrometria de massas, ressonância magnética nuclear uni e bidimensional, além de comparação com dados espectrais descritos na literatura.

A phytochemical investigation of the roots of Krameria tomentosa A. St. -Hil. led to the isolation of five neolignans, two of them with novel structures [1,1'-(E)-propenyl-4-methoxy3,4'-oxyneolignan (ottomentosa) and 2-(2'-hydroxy-4',6'-dimethoxyphenyl)benzofuran5-carboxylic acid (sobraline)] and three known compounds [eupomatenoid 6, dihydrocarinatidin and 2-(2',4'-dihydroxyphenyl)-5-(E)-propenylbenzofuran]. The structural characterization of the compounds isolated was established based on infrared spectroscopy, mass spectrometry, one-and two-dimensional nuclear magnetic resonance, along with comparison with spectral data described in the literature.

An atisane diterpene was isolated from Xylopia langsdorfiana St. Hilaire & Tulasne, Annonaceae, leaves, ent-atisane-7α,16α-diol (xylodiol). Preliminary study showed that xylodiol was cytotoxic and induced differentiation on human leukemia cell lines. However, the molecular mechanisms of xylodiol-mediated cytotoxicity have not been fully defined. Thus, we investigated the anti-tumor effect of xylodiol in human leukemia HL60 cell line. Xylodiol induced apoptosis and necrosis. HL60 cells treated with xylodiol showed biochemical changes characteristic of apoptosis, including caspases-8, -9 and -3 activation and loss of mitochondrial transmembrane potential (∆ Ψm). However, there was a condensation rather than swelling of mitochondria. Moreover, the formation of condensed mitochondria and the loss of ∆ Ψm occurred downstream of caspase activation. Cyclosporine A did not protect HL60 cells from the cytotoxic effects of xylodiol, suggesting that the loss of ∆ Ψm is a late event in xylodiol-induced apoptosis. Oxidative stress was involved in xylodiol-induced apoptosis. Thus, we conclude that activated caspases cleave cellular proteins resulting in mitochondrial damage leading to mitochondrial condensation, loss of ∆ Ψm and ROS release from the mitochondria. ROS can further induce and maintain a collapse of ∆ Ψm leading to cellular damage through oxidation of lipids and proteins resulting in apoptotic cell death.

A análise fitoquímica das partes aéreas de Cordia globosa, coletadas no município de Picuí, PB, Brasil, resultou no isolamento e identificação estrutural da 7,4'-dimetilnarigenina (0,025 g) e eriodictiol (0,015 g). Estas duas flavanonas são as primeiras agliconas, desta classe, isoladas no gênero Cordia.

The phytochemical analysis of aerial parts of Cordia globosa, collected in the Municipality of Picuí, State of Paraíba, Brazil, resulted in the isolation and structural identification of narigenin-4',7-dimethyl ether (0.025 g) and eriodictyol (0.015 g). These compounds are the first flavanones aglycones isolated from the genus Cordia.

Pradosia huberi (Ducke) Ducke (Sapotaceae), espécie Amazônica popularmente conhecida como "casca-doce" é utilizada na medicina tradicional no tratamento de gastrite. O extrato etanólico de suas cascas é rico em polifenóis que podem apresentar um grande número de atividades, incluindo efeito vasorelaxante e cardioprotetor. O objetivo deste estudo foi avaliar as propriedades farmacológicas do extrato etanólico (EPH), de frações e da 2,3-diidromiricetina-3-O-α-L-raminosídeo isolados de P. huberi, em artéria mesentérica isolada de rato. O EPH foi fracionado resultando nas seguintes frações: CHCl3, CHCl3:AcOEt (1:1), AcOEt, AcOEt:MeOH (1:1) e MeOH. Da fração MeOH foi isolada a 2,3-diidromiricetina-3-O-α-L-raminosídeo e identificada através de espectro de RMN de ¹H e 13C, além de comparações com os dados de literatura. EPH (1-100 µg/mL) promoveu relaxamento dependente de concentração no tônus vascular induzido por 10 µM de fenilefrina (CE50=17,1±2,9 µg/mL; Emax=87,4±2,9 %, n=8). A fração MeOH também relaxou os anéis mesentéricos (CE50=31±2,0µg/mL; Emax=54±12,5%, n=6), porém com menor eficácia quando comparado ao efeito de EPH. Tanto o efeito de EPH com de MeOH foram completamente abolidos após a remoção do endotélio vascular. A fração AcOEt:MeOH (1:1) e o flavonoide isolado induziram vasorelaxamento. O estudo demonstrou que o EPH e a fração MeOH de Pradosia huberi apresentam propriedade vasorelaxante que pode ser completamente dependente da presença do endotélio. O flavonoide isolado não é o responsável por este efeito vasorelaxante.

Pradosia huberi (Ducke) Ducke (Sapotaceae), an Amazonian species, is popularly known as "casca-doce" and used in the folk medicine for the treatment of gastritis. The ethanol extract of the bark contains mainly polyphenolic compounds, which are known to show a large number of activities, including cardioprotective and vasorelaxant effects. The aim of this study was to evaluate the pharmacological properties induced by P. huberi ethanol extract (PHEE) and fractions and 2-3-dihydromyricetin-3-O-α-L-rhamnoside derived from this extract, in isolated rat mesenteric arteries. PHEE was separated and the following fractions were obtained: CHCl3, CHCl3:AcOEt (1:1), AcOEt, AcOEt:MeOH (1:1) and MeOH. We isolated 2-3-dihydromyricetin-3-O-α-L-rhamnoside from the MeOH fraction, which was identified by¹H and 13C NMR spectra and compared with data in the literature. PHEE (1-100 µg/mL) induced concentration-dependent relaxations of 10 µM phenylephrine-induced tone (EC50=17,1±2,9 µg/mL; Emax=87.4±2.9 %, n=8). The MeOH fraction also relaxed mesenteric rings (EC50=31±2.0 µg/mL; Emax=54±12.5%, n=6) but less effectively when compared to PHEE. Both effects were completely abolished after removal of the vascular endothelium. The AcOEt:MeOH (1:1) fraction and the isolated flavonoid were ineffective in eliciting vasorelaxation. The study demonstrates that PHEE and MeOH fraction of Pradosia huberi possess a vasorelaxant effect, which may be completely dependent upon endothelium. The isolated flavonoid is not responsible for this vasorelaxant effect.

A isquemia renal está presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. O objetivo deste trabalho foi avaliar a integridade e a função renal de cães submetidos à isquemia e reperfusão com ou sem aplicação de clorpromazina. Para tanto foram utilizados 12 cães distribuídos aleatoriamente em dois grupos de seis indivíduos: grupo A com isquemia e reperfusão sem tratamento por clorpromazina e o grupo B com isquemia e reperfusão tratados previamente com clorpromazina. De cada cão foi coletado sangue e urina antes da isquemia, no inicio da reperfusão, após 120 minutos de reperfusão e semanalmente até 28º dia pós-cirúrgico para verificar possíveis efeitos tardios da isquemia/reperfusão. Avaliações da integridade e função renal foram feitas por exame físico, concentração sérica de ureia e creatinina e determinação da GGT urinária. A avaliação da relação proteína urinária/creatinina urinária (PU/CU) e atividade da GGT urinária são exames mais sensíveis para detectar lesão tubular aguda que o exame de urina de rotina, uma vez que estas variáveis apresentaram alteração mais precocemente. Não houve ação protetora da clorpromazina conforme constatado por meio da urinálise, dosagens séricas de ureia e creatinina, excreção urinária de GGT e PU/CU.

Renal ischemia may occur in different situations such as vascular or renal surgery and also in renal transplantation. This study evaluates renal function in dogs submitted to ischemia and reperfusion after chlorpromazine application. Twelve adult mongrel dogs were distributed into two groups with six animals each. Group A was composed of dogs submitted to renal ischemia and reperfusion without previous administration of chlorpromazine. Group B was composed of dogs with renal ischemia and reperfusion previously treated with chlorpromazine. In order to evaluate the possible ischemia/reperfusion late effects, blood and urine samples were sampled in four different times: Before ischemia, early stages of reperfusion, 120 minutes after reperfusion, and every week until 28th day postsurgery. Renal function was evaluated by clinical examination, serum urea and creatinine levels and urinary GGT activity. PU/CU and GGT urinary activity were more sensitive in detecting acute tubular injury than routine urine examination because these variables showed earlier changes. Based on urinalysis, urea and creatinine serum levels plus urinary excretion of GGT and PU/CU, no evidences of protective action of chlorpromazine were observed.

Malária é uma doença parasitária humana causada por protozoários do gênero Plasmodium. Esta doença tem acometido populações que habitam regiões tropicais e subtropicais. Anualmente, cerca de 500 milhões de casos ocorrem no mundo, o que permite ser considerada uma doença emergente de importância para a saúde pública. Neste contexto, os produtos naturais, a exemplo das espécies vegetais, têm suas moléculas bioativas como alvo para estudos farmacológicos, toxicológicos e fitoquímicos destinados à síntese de medicamentos mais eficazes para o tratamento de inúmeras doenças. Portanto, este trabalho fornece subsídio às pesquisas com produtos naturais para o tratamento da malária. Nesta revisão, 476 espécies de plantas do continente Americano foram relatadas para a atividade antimalárica, sendo destas 198 ativas e 278 inativas para algum tipo de Plasmodium, quando avaliados através de modelos in vitro e in vivo.

Malaria is a human parasitic disease caused by protozoa species of the Plasmodium genus. This disease has affected populations of the tropical and subtropical regions. About 500 million new cases occur annually on the world and therefore it is considered an emerging disease of important public health problem. In this context, the natural products as vegetables species have their bioactive molecules as targets for pharmacological, toxicological and phytochemical studies towards the development of more effective medicines for the treatment of many diseases. So this work intends to aid the researchers in the study of natural products to the treatment of malaria. In this review, 476 plants of the American continent were related for the antimalarial activity and of these vegetables species 198 were active and 278 inactive for some type of Plasmodium when they were evaluated through of in vitro or in vivo bioassays models.