Atividade antiinflamatória intestinal e antiulcerogênica gástrica e duodenal de Hymenaea stigonocarpa Mart. ex Hayne

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Structure-activity relationship of compounds which are anti-schistosomiasis active

O método do orbital molecular AM1 foi empregado para calcular um conjunto de descritores moleculares para vinte neolignanas sintéticas com atividade anti-esquistossomose. O método de reconhecimento de padrão (análise de componentes principais ACP, análise de conglomerados AC e análise de discriminante) foi utilizado para obter a relação entre a estrutura molecular e a atividade biológica. O conjunto de moléculas foi classificado em dois grupos de acordo com seus graus de atividade biológica. Estes resultados permitem que, projete-se racionalmente novos compostos, potenciais candidatos à síntese e à avaliação biológica.

Extratos padronizados para o tratamento de doenças crônicas: Arrabidaea spp

Pós-graduação em Química - IQ

Effect of menthol in experimentally induced ulcers: Pathways of gastroprotection

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

Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of annona sylvatic

Background The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. Methods The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg-1 of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. Results Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. Conclusions Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8 μg/mL (827.28 μM) and 209.9 μg/mL (328.48 μM), respectively. The acute administration of the EAF fraction in doses of 500, 1000, and 2000 mg · kg-1 of body weight did not cause signs of toxicity in the treated animals.

Caracterização por espectrometria de massas e investigação das atividades anti-inflamatória e gastroprotetora do extrato etanólico e diterpenos clerodânicos de folhas de Casearia sylvestris Swartz

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização por espectrometria de massas e investigação das atividades anti-inflamatória e gastroprotetora do extrato etanólico e diterpenos clerodânicos de folhas de Casearia sylvestris Swartz

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Sesquiterpene Lactones with Anti-Hepatitis C Virus Activity Using Molecular Descriptors

Hepatitis C is a worldwide public health problem. The available therapies are limited by their partial effectiveness and with meaningful side-effects. Sesquiterpene lactones (SLs) are a group of natural products with a wide variety of chemical structures and biological activities associated. There are few studies about the influence of the molecular structure of SLs for the anti-hepatitis C virus activity. In the present work, SLs are investigated in a subgenomic RNA replicon assay system and were analyzed using multiple linear regression along with self-organizing maps with DRAGON descriptors in order to identify the structural requirements for their biological activity and to predict the inhibitory potency of SLs. Characteristics such as stereochemistry and electronic effects demonstrated to be important for their anti-HCV activity, and the SOM produced a clear separation betwenn active and inactive compounds. Therefore, it is possible to use this map as a filter for virtual screening to predict the anti-HCV activity of SLs.

Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI) assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ), a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

Bromelain's activity and potential as an anti-cancer agent:Current evidence and perspectives

The medicinal qualities of pineapple are recognized in many traditions in South America, China and Southeast Asia. These qualities are attributed to bromelain, a 95%-mixture of proteases. Medicinal qualities of bromelain include anti-inflammatory, anti-thrombotic, fibrinolytic and anti-cancer functions. Existing evidence derived from clinical observations as well as from mouse- and cell-based models suggests that bromelain acts systemically, affecting multiple cellular and molecular targets. In recent years, studies have shown that bromelain has the capacity to modulate key pathways that support malignancy. It is now possible to suggest that the anti-cancer activity of bromelain consists in the direct impact on cancer cells and their micro-environment, as well as in the modulation of immune, inflammatory and haemostatic systems. This review will summarize existing data relevant to bromelain's anti-cancer activity and will suggest mechanisms which account for bromelain's effect, in the light of research involving non-cancer models. The review will also identify specific new research questions that will need to be addressed in order for a full assessment of bromelain-based anti-cancer therapy.

In vitro anti-canine distemper virus activity of fucoidan extracted from the brown alga Cladosiphon okamuranus

Canine distemper virus (CDV) is a morbillivirus related to measles virus that infects dogs and other carnivores. CDV has a significant global impact on animal health; however, there is no current antiviral treatment for CDV infection. In recent years, it has been demonstrated that sulfated polysaccharides exhibit antiviral properties both in vivo and in vitro, despite their low cytotoxicity to host cells. Fucoidan is a sulfated polysaccharide found in the cell wall matrix of brown algae. In this study, we evaluated in vitro anti-CDV activity of fucoidan, which was derived from Cladosiphon okamuranus. Fucoidan actively inhibited CDV replication in Vero cells at a 50% inhibitory concentration (IC50) of 0.1 lg/ml. The derived selectivity index (SI50) was[20,000. This polysaccharide likely inhibits viral infection by interference in the early steps and by inhibiting CDV-mediated cell fusion. Fucoidan may be useful in development of pharmacological strategies to treat and control CDV infection.

Vegetables containing phytochemicals with potential anti-obesity properties: A review

The incidence of obesity is rising worldwide at an alarming rate and is becoming a major public health concern with incalculable social and economic costs. Studies have exposed the relationship between the adiposity, inflammation and the development of other metabolic disorders, so dietary factors that influence some or all of these are of interest. Dietary phytochemicals appear to be able to target different stages of the adipocyte (fat cell) lifecycle. For example, several classes of polyphenols have been implicated in suppressing the growth of adipose tissue through modifying the adipocyte lifecycle. Many dietary phytochemicals also have strong anti-inflammatory activity, but the amount present in plants varies and may be affected by processing. In this review we summarise the likely mechanisms of action of plant phytochemicals. We highlight the major vegetable sources of polyphenols, including those with possible synergistic attributes, discuss the variation in polyphenol levels and their distribution in cultivars and outline the effects of food processing. The identification and characterisation of the anti-obesogenic properties of phytochemicals in vegetables, as well as an appreciation of the effect of cooking on phytochemical content provide significant new information supporting dietary guidelines that encourage vegetable consumption for the prevention and management of lifestyle related disease.

Evaluation of anti-inflammatory potential of Chloranthus erectus (Buch.-Ham.) Verd. leaf extract in rats

Aim of the study: Chloranthus erectus (Buch.-Ham.) Verdcourt (Chloranthaceae) is a shrub native to tropical and temperate zone of Eastern Himalaya of India and South-East Asia and have traditionally been used as a folklore medicine to treat localised swelling, joint pain, skin inflammation, fever and bodyache. In this study, an attempthas been made to demonstrate the anti-inflammatory activity of methanol extract obtained from Chloranthus erectus leaves (MECEL) in acute, sub-acute and chronic mouse models. Materials and methods: Inflammation in the hind paw of Wistar albino rat was induced by carrageenan, histamine and serotonin, and tissue granuloma pouch was induced by cotton pellet method. Antiinflammatory drug-phenylbutazone was used as standard drug for comparison. Results: In acute carrageenan-induced rat hind paw edema, oral administration of MECEL at 200 mg/kg produced significant inhibition of edema by 38.34 % (p<0.01) while the histamine- and serotonin-induced sub-acute model, the inhibition of paw edema reached 52.54 % (p < 0.001) and 25.5 % (p < 0.01), respectively. in a 7-day study, MECEL at 20 and 50 mg/kg produced significant suppression of cotton pellet-induced tissue granuloma formation in rats. Conclusions: This preliminary study revealed that the methanol extract of Chloranthus erectus exhibited significant anti-inflammatory activity in the tested models, and may provide the scientific rationale for its popular folk medicine as anti-inflammatory agent.

Transition metal complexes of 3-aryl-2-substituted 1,2-dihydroquinazolin-4(3H)-one derivatives: New class of analgesic and anti-inflammatory agents

Five-coordinate, neutral transition metal complexes of newly designed pyridine-2-ethyl-(3-carboxyhdeneamino)-3-(2-phenyl)-1,2-dihydroquinazoli n-4(3H)-one (L) were synthesized and characterized The structure of ligand is confirmed by single crystal X-ray diffraction studies The compounds were evaluated for the anti-inflammatory activity by carrageenan-induced rat paw edema model while their analgesic activity was determined by acetic acid-induced writhing test in mice wherein the transition metal complexes were found to be more active than the free ligand (C) 2010 Elsevier Masson SAS All rights reserved.

Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as anti-cancer agents

A series of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles 9a-j were obtained via multistep synthesis from hydroxybenzophenones 4a-e. The cytotoxicity of compounds 9a-j was evaluated against human leukemia cell lilies (K562 and CEM). The compounds exhibited moderate to good anti-cancer activity with compounds 9b and 9i having a chloro group exhibiting the best activity (IC50 = 10 mu M). Compound 9i exhibited activity against both the cell lines and 9b only exhibited activity against CEM. Further, a lactate dehydrogenase (LDH) assay and DNA fragmentation studies of the compounds 9a-j were also performed. (C) 2013 Elsevier Masson SAS. All rights reserved.