Search

O presente estudo teve como objetivo reisolar, identificar e investigar o potencial antifitopatogênico de uma série de metabólitos secundários obtidos de duas fontes botânicas diversas. Do extrato acetônico de Usnea steineri , foram obtidos ácido úsnico e ácido difractáico. A partir do extrato de Rosmarinus officinalis , o ácido rosmarínico foi reisolado. A identificação de todas as substâncias foi realizada com base em dados obtidos de 1 H RMN, 13 C RMN e/ou comparação com padrões autênticos. Nos testes de atividade antimicrobiana contra nove bactérias fitopatogênicas, o ácido úsnico se mostrou promissor, sendo que os melhores resultados obtidos foram contra as bactérias Xanthomonas axonopodis e Xanthomonas campestriscom MIC de 3,12 µg/mL e 6,25 µg/mL, respectivamente. Nos estudos de sobrevivência realizados com o ácido úsnico contra Xanthomonas axonopodis constatou-se que na concentração de 3,12 µg/mL somente após 48 horas, o ácido úsnico foi bactericida para as espécies estudadas. Os resultados da avaliação da atividade citotóxica do ácido úsnico em células GM7492A (fibroblastos humanos) revelaram que não houve diferenças significativas entre as culturas tratadas com ácido úsnico (15,6 µg/ml a 2000,0 µg/ml) e o controle negativo, apresentando ausência citotóxica efeitos nas concentrações testadas. Diante dos resultados, pode-se concluir que o ácido úsnico é um composto promissor para o desenvolvimento de um novo bactericida para o controle de alguns fitopatógenos.

Neglected tropical diseases are significant causes of death and temporary or permanent disability for millions living in developing countries. Unfortunately, there is no effective treatment for these diseases. Thus, this work aimed to conduct a chemical analysis using HPLC/UV and GC/MS to identify the major constituents of the hydroalcoholic extracts of Capsicum frutescens and Capsicum baccatum fruits, evaluating these extracts and their constituents’ schistosomicidal, leishmanicidal and trypanocidal activities. The results obtained for the extracts of C. frutescens are better when compared to those obtained for C. baccatum, which can be related to the different concentrations of capsaicin (1) present in the extracts. The lysis of trypomastigote forms results for capsaicin (1) led to a significant value of IC50 = 6.23 µM. Thus, the results point to capsaicin (1) as a possible active constituent in these extracts.

Origanum vulgare, known for its medicinal value, is officially accepted in many countries. The flowers and leaves are used globally in homeopathy. In Brazilian folk medicine, O. vulgare has been used to treat diabetes mellitus. This study evaluated the hypoglycemic activity of an infusion extract (RosCE) of commercially available O. vulgare leaves in alloxan-induced diabetic rats. Oral administration of RosCE resulted in the reduction of blood glucose levels after the first day of treatment, compared to the diabetic control group. These results showed that RosCE displays hypoglycemic activity, which may be due to the combined effect of rosmarinic acid, and other minor compounds. Reversed phase-high performance liquid chromatography-diode array detection was used to identify and quantify the major constituents of RosCE. This study presents evidence that supports the folkloric use of O. vulgare for the treatment of hyperglycemia, confirming the use of its infusion as an antidiabetic herbal medicine.

The sol–gel process emerges as an interesting strategy to obtain hybrid materials (organic–inorganic materials), it takes place under mild conditions and can produce nanoparticles with different shapes and sizes, leading to composite materials with multifunctional properties. In this paper will describe the synthesis and characterization of the mesoporous silica obtained by the sol–gel process as well as their potential applications as antimicrobial agents, biological markers, odontology, and others. Highly ordered mesoporous silica has gained attention from scientists because it exhibits large specific area and pore volume as well as low density. The preparation of mesoporous silica matrixes via the sol–gel process by using the surfactant cetyltrimethylammonium bromide and the copolymer Pluronic P-123 as structure-driving agents. The results revealed that samples V and VII behaved the most efficiently. Log10 CFU/mL decreased by more than two digits for Candida albicans, Staphylococcus aureus, and Streptococcus mutans and was statistically significant for all the tested microorganisms. Therefore, this study demonstrated that the functionalized mesoporous silica is a viable antimicrobial agent when it is incorporated into dental acrylic resin.

Struthanthus siringifolius Mart. (Loranthaceae) e uma especie do Cerrado brasileiro conhecida como “erva de passarinho”. E popularmente usada para tratar tuberculose e problemas pulmonares. Esta especie e raramente estudada no Brasil e seu perfil quimico e potencial farmacologico sao pouco conhecidos. Neste trabalho relatamos o isolamento do triterpeno lupano 7β, 15α-di-hidroxi-lup-20- (29) -eno-3β- O -palmitato ( 1 ) do extrato etanolico das partes aereas de S. siringifolius . Na dose de 200 μM, este triterpeno diidroxilado matou 25 e 50% dos vermes adultos de Schistosoma mansoni em 48 e 72 h, respectivamente. Adicionalmente, nas doses de 25 e 50 μM, esse mesmo triterpeno diminuiu significativamente a atividade motora dos vermes adultos de S. mansoni . Esses resultados sugerem que os triterpenos do tipo lupano podem estar associados a atividade esquistossomicida de S. Syringifolius e devem ser considerados para estudos antiparasitarios adicionais.

Copaifera pubiflora Benth oleoresin (CPO) is used as an anti-inflammatory, wound healing, and antimicrobial. This paper reports the cytotoxic, anti-inflammatory, and antinociceptive activities of CPO. CPO (10 mg/kg) did not affect locomotor capacity in the open-field and rotarod tests and was not cytotoxic to CHO-k1, THP-1, and L929 cell lines. It was active in the formalin test at 3 mg/kg by 86 ± 3% and 96 ± 3%, respectively, for the first and second phases. At 10 mg/kg, CPO inhibited 90 ± 7%, the pain in the mechanical hyperalgesia test. In the tail-flick test, CPO at 3 mg/kg affected the tail-flick latencies in mice by 77 ± 20%, which in combination with naloxone was only partially reduced. At 3 mg/kg CPO inhibited 80 ± 12% the carrageenan-induced paw edema, and at 3 mg/kg it reduced by 91 ± 5% the nociception on acetic acid-induced abdominal writhing. Therefore, CPO possesses anti-inflammatory and antinociceptive activities.

Ambuic acid (AA) is a highly-modified cyclohexenone and known as a promising inhibitor of quorum sensing in methicillinresistant Staphylococcus aureus, and is thus a candidate as an antivirulence drug. This molecule is mainly produced by the species of Pestalotiopsis and, since its discovery twenty years ago, only a restricted amount of AA-derivatives have been described. Despite being a promising subject, methods for the analysis of modified AA-analogues via mass spectrometry remain unexplored. In order to adress this question, the marine fungus Pestalotiopsis sp. 4A11 associated with the ascidian Didemnum perlucidum was grown in a solid rice medium and its crude extract was chemically studied. From this extract, AA and 10-hydroxy ambuic acid (10-HAA) were isolated and identified using NMR spectroscopy with the aim of obtaining model compounds for the MS analysis. These served as reference compounds (seeds) to guide the dereplication of other AA-analogues via LC-MS/MS-based molecular networking. Based on the manual interpretation of the fragmentation pathways of the seeds and related compounds observed in the networks, six AA-derivatives were dereplicated in the extract. Furthermore, three analogues with unprecedented chemical formulas were proposed as putative unprecedented AA-derivatives. The fragmentation annotation proposed represents a fast and feasible method for characterizing AA-derivatives.

Made available in DSpace on 2022-04-29T08:36:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 This work aimed to synthesize poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles containing hinokinin (HNK) and to evaluate their cytotoxic activity against tumoral SiHa cells and non-tumoral HaCaT cells. Hinokinin was incorporated into PLGA (PLGA-HNK) with an encapsulation efficiency of 84.18 ± 2.32%. PLGA and PLGA-HNK were characterized by SEM microscopy and showed spherical morphology with an average size of ∼3.33. Encapsulation efficiency was determined by a calibration curve using UV-vis spectroscopy. PLGA-HNK more active inhibiting proliferation of SiHa cells (IC50 = 14.68 µM) than free HNK (IC50 = 225.5 µM). In relation to HaCaT cells, PLGA-HNK showed no significant difference compared to the negative control. These results led to an increase in HNK bioavailability and thereby, biological activity. In silico prediction analysis suggests that HNK is cytotoxic against SiHa cells with E6 and MDM2 inhibition as possible main mechanism of action. Departamento de Física e Química Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista Departamento de Biologia e Zootecnia Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista Núcleo de Pesquisa em Ciências Exatas e Tecnológicas Universidade de Franca Centro Universitário Departamento de Física e Química Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista Departamento de Biologia e Zootecnia Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista

Made available in DSpace on 2022-04-29T08:29:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The genus Absidia is widely used in the biotransformation of different classes of natural products. This study evaluates the ability of the Absidia coerulea 3A9 marine derived strain isolated from the ascidian Distaplia stilyfera to perform biotransformations by conducting assays with (–)-cubebin, as substrate. The experiment was optimized using the experimental design proposed by Plackett–Burman for seven factors and eight experiments, to establish the biotransformation conditions that would allow maximum production of biotransformed dibenzylbutyrolactone (–)-hinokinin. An analytical method based on Reverse-Phase-High Performance Liquid Chromatography (RP-HPLC) was developed to quantify the fungal biotransformation product. The factor that influenced the (–)-hinokinin peak area the most positively was the percentage of seawater (%seawater) given that its %relative standard deviation (%RSD) showed a 32.92% deviation from the real value. Center for Research in Exact and Technological Sciences University of Franca Department of Botany and Ecology Biosciences Institute Federal University of Mato Grosso Center for Natural and Human Sciences Federal University of ABC Department of Drugs and Medicines School of Pharmaceutical Sciences University Estadual Paulista Department of Drugs and Medicines School of Pharmaceutical Sciences University Estadual Paulista CAPES: 001 FAPESP: 2014/19184-7 FAPESP: 2017/14261-1 CAPES: 23038.009588/2013-68 CSF-PVEs 27/2014 CNPq: 302340/2018-1

Phytochemicals have been suggested as an effective strategy for cancer prevention. Within this context, triterpene betulinic acid (BA) exhibits several biological properties but its chemopreventive effect has not been fully demonstrated. The present study investigated the antigenotoxic potential of BA against doxorubicin (DXR)-induced genotoxicity using the mouse peripheral blood micronucleus assay, as well as its anticarcinogenic activity against 1,2dimethylhydrazine (DMH)-induced colorectal lesions in rats. Micronuclei (MN) assay and aberrant crypt foci assay were used to assess the antigenotoxic and the anticarcinogenic potential, respectively. The molecular mechanisms underlying the anticarcinogenic activity of BA were evaluated by assessing anti-inflammatory (COX-2) and antiproliferative (PCNA) pathways. The results demonstrated that BA at the dose of 0.5 mg/kg bodyweight exerted antigenotoxic effects against DXR, with a reduction of 70.2% in the frequencies of chromosomal damage. Animals treated with BA showed a 64% reduction in the number of preneoplastic lesions when compared to those treated with the carcinogen alone. The levels of COX-2 and PCNA expression in the colon were significantly lower in animals treated with BA and DMH compared to those treated with the carcinogen alone. The chemopreventive effect of BA is related, at least in part, to its antiproliferative and anti-inflammatory activity, indicating a promising potential of this triterpene in anticancer therapies, especially for colorectal cancer.

The ethanol crude extract from cashew (Anacardium occidentale L. Anacardiaceae) displayed significant antiplasmodial activity (IC50 0.577 μg/ml). Liquid chromatography-high resolution Mass spectrometry analysis was performed to identify the main compounds existing in the ethanol extract. The occurrence of anacardic acids, cardols, and 2-methylcardols derivatives was confirmed in the extract. The IC50 obtained, when the main isolated compounds were evaluated in Plasmodium falciparum D6 strain, ranged from 5.39 μM to >100 μM. Tested here for the first time, the data showed that cardol triene 1 (IC50 = 5.69 μM) and 2-methylcardol triene 4 (IC50 = 5.39 μM) demonstrated good antimalarial activity. In conclusion, Anacardium occidentale nuts presented relevant biological potential, and further studies should be considered. Keywords: Anacardic acid, Antiplasmodial, Cardol, Cashew, Methylcardol

Piper cubeba L. f. is a food seasoning, which contains secondary metabolites displaying several biological properties, such as cytotoxic, anti-inflammatory, and antiparasitic activities. The lignans (+)-dihydroclusin, (-)-clusin, (-)-cubebin, (-)-yatein, and (-)-haplomyrfolin were isolated, with (-)-haplomyrfolin reported for the first time in P. cubeba seeds. Chromatographic standards were used to develop a reliable reverse-phase high-performance liquid chromatography analytical method according to the Agência Nacional de Vigilância Sanitária and International Conference on Harmonization guidelines to quantitate these lignans in both P. cubeba seeds and their extracts. The extraction of the lignans was also optimized, with the best conditions being ultrasound-assisted extraction, with 84% aqueous ethanol for 38 min in a single extraction. This procedure allows for the extraction of more than 80% of the total lignans, which is better in comparison to other techniques, such as maceration and Soxhlet extraction.

In this study, the trypomastigotes of a Y strain of Trypanosoma cruzi were inoculated intraperitoneally into male BALB/c mice weighing approximately 25 g each, which were divided into groups for evaluation of the trypanocidal activity. For the treatment of experimental groups, encapsulated and unencapsulated (-)-cubebin, Benznidazole, and two groups as negative controls were used. The encapsulated (-)-cubebin showed a 68.1 % encapsulation efficiency. The parasitemia peak of substances remained around the 9th day after the observed reduction in the number of circulating trypomastigotes. The encapsulated (-)-cubebin and (-)-cubebin unloaded showed a decrease of 61.3 % and 58.5 % in the number of parasites as compared to the negative control, respectively. Moreover, animals treated with encapsulated (-)-cubebin had a higher survival time as compared to the other groups. In conclusion, the results obtained were more promising for encapsulated (-)-cubebin as compared to unloaded particles.

Chemical investigation into the ethyl acetate extract of the endophytic fungus Corynespora olivacea (V18) associated with Vochysia divergens identified compounds 1 and 2. The compounds were characterized by spectroscopic methods including NMR (1D and 2D) and HRMS. The cytotoxicity of the crude extract and the isolated compounds against normal human lung fibroblast cells, lineage GM07492A, was evaluated by the XTT assay. To the best of our knowledge, this is the first chemical and biological screening of the cytotoxicity of C. olivacea derived from V. divergens.

This study analyzes the antileishmanial activity of the crude ethanol extract, fractions, and isolated compounds of A. othonianum nuts. Antileishmanial activity was evaluated against Leishmania amazonensis promastigotes in vitro. The phytochemical study was performed by high-performance liquid chromatography-high-resolution mass spectrometry-diode array detector (HPLC-HRMS-DAD) and by preparative HPLC. HPLC-HRMS-DAD analysis of the bioactive extract confirmed the presence of ten alkyl phenol derivatives that had previously been isolated from A. occidentale. Bioassay-guided isolation afforded cardanol triene, cardanol diene, cardanol monoene, cardol triene, anacardic acid triene, anacardic acid diene, and anacardic acid monoene. Cardol triene gave an IC50 of 80.66 µM. The obtained data suggest that the evaluated extract, fractions, and cardol triene had moderate activity against L. amazonensis promastigotes. This is the first description of alkyl phenols in A. othonianum. Este estudo visou avaliar a atividade antileishmanial do extrato bruto etanólico, frações e substâncias isoladas obtidos das castanhas de A. othonianum. A atividade antileishmania foi avaliada por ensaio in vitro nas formas promastigotas de Leishmania amazonensis. O estudo fitoquímico foi realizado por cromatografia líquida de alta eficiência - espectrometria de massa de alta resolução - detector de arranjo de diodos (CLAE-EMAR-DAD) e por CLAE-preparativa. A análise por CLAE-EMAR-DAD do extrato bioativo confirmou a presença de dez derivados de alquil-fenóis previamente isolados de A. occidentale. A investigação bioguiada resultou no isolamento do cardanol trieno, cardanol dieno, cardanol monoeno, cardol trieno, ácido anacárdico trieno, ácido anacárico dieno e ácido anacárico monoeno. O cardol trieno apresentou uma CI50 de 80,66 µM. Os dados obtidos sugeriram que o extrato, frações e o cardol trieno possuem atividade moderada no ensaio nas formas promastigotas de L. amazonensis. Este é o primeiro relato de alquil-fenóis em A. othonianum.

Despite the current treatments against Chagas Disease (CD), this vector-borne parasitic disease remains a serious public health concern. In this study, we have explored the in vitro and/or in vivo trypanocidal and cytotoxic activities of the essential oils (EOs) obtained from Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) (DA-EO), Lippia alba (Mill.) N.E. Brown (Verbenaceae) (LA-EO), and Tetradenia riparia (Hochst.) Codd (Lamiaceae) (TR-EO) grown in Brazil Southeast. DA-EO was the most active against the trypomastigote and amastigote forms in vitro; the IC50 values were 8.7 and 12.2 μg mL-1 , respectively. The EOs displayed moderate toxicity against LLCMK2 cells, but the DA-EO showed high selectivity index (SI) for trypomastigote (SI=33.2) and amastigote (SI=11.7) forms. Treatment with 20 mg/kg DA-EO, LA-EO, or TR-EO for 20 days by intraperitoneal administration reduced parasitemia by 6.36 %, 4.74 %, and 32.68 % on day 7 and by 12.04 %, 27.96 %, and 65.5 % on day 9. These results indicated that DA-EO, LA-EO, and TR-EO have promising trypanocidal potential in vitro, whereas TR-EO has also potential trypanocidal effects in vivo.

Made available in DSpace on 2022-04-29T08:36:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 The objective of the present study was to evaluate the action of the crude hydroalcoholic extract of Piper cubeba fruits and isolated lignans (cubebin, dihydrocubebin, ethylcubebin, hinokinin and methylcubebin) on head and neck cancer cells. We evaluated the influence of the Piper cubeba extract and isolated lignans (10, 50 e 100 μg/mL) for 4, 24, 48 and 72 h, in the larynx (Hep-2) and oral (SCC-25) squamous cell carcinoma cells and normal fibroblasts, on morphology, cell proliferation and migration, cytotoxicity, genotoxicity and gene and protein expression (PTGS2, PTGER3, PTGER4, MMP2, MMP9). The results showed that the P. cubeba extract and different lignans do not alter the cellular morphology, but decrease cell proliferation and migration, have low cytotoxic and genotoxic effects, probably due to the alteration of the expression of genes and proteins involved with inflammatory process. From these data, we can conclude that the lignans cubebin and methylcubebin had a greater effect on head and neck cancer cells in the antiproliferative, antimigratory and genotoxic action, and could be the target of the development of new therapies including possible new drugs as a therapeutic resource for the treatment of head and neck cancer due to its immense range of biological properties. São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Science (IBILCE) Campus São José do Rio Preto Department of Biology School of Medicine of São José do Rio Preto (FAMERP) Department of Molecular Biology Department of Genetics and Evolutive Biology Institute of Biosciences University of São Paulo University of Franca (UNIFRAN) Nucleus of Research in Exact and Technological Sciences São Paulo State University (UNESP) School of Engineering (FEIS) Campus Ilha Solteira Department of Physical Chemistry São Paulo State University (UNESP) School of Engineering (FEIS) Campus Ilha Solteira Department of Biology and Animal Science São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Science (IBILCE) Campus São José do Rio Preto Department of Biology São Paulo State University (UNESP) School of Engineering (FEIS) Campus Ilha Solteira Department of Physical Chemistry São Paulo State University (UNESP) School of Engineering (FEIS) Campus Ilha Solteira Department of Biology and Animal Science

Uma das principais doencas tropicais negligenciadas e a doenca de Chagas (DC), causada pelo Trypanosoma cruzi. No Brasil, a regiao de alta prevalencia da doenca abrange uma area que vai do Maranhao ate o Rio Grande de Sul. O tratamento da DC e feito normalmente com os antiparasitarios Benzonidazol e Nifurtimox que possui diversos efeitos colaterais. O mercado de produtos naturais vem crescendo a cada ano e a utilizacao de plantas tem se destacado como alternativa para desenvolvimento de novos medicamentos para cura dessa doenca. Neste contexto o presente trabalho descreve o estudo quimico dos oleos essenciais das folhas de Zanthoxylum riedelianum, Zanthoxylum rhoifolium e Kielmeyera coriacea e dos frutos da Xylopia aromatica e Zanthoxylum rhoifolium, bem como a capacidade tripanocida e efeitos citotoxicos dos mesmos. O material vegetal foi coletado no municipio de Ipora-GO e submetidos a hidrodestilacao em aparelho tipo Clevenger para obtencao dos oleos essenciais. As analises quimicas dos oleos foram realizadas em cromatografo gasoso acoplado em espectrometro de massas. Para a realizacao do ensaio da atividade tripanocida formas tripomastigotas foram adicionados em placa de microtitulacao de 96 pocos e posteriormente adicionados os oleos essenciais e apos 24 horas de incubacao, foi realizada a verificacao da atividade biologica atraves da quantificacao direta dos parasitas vivos em câmara de Neubauer levando em consideracao a motilidade flagelar dos protozoarios. Para a avaliacao da atividade citotoxica fibroblastos da linhagem LLCMK2 foram adicionados em placa de microtitulacao de 96 pocos e posteriormente adicionados os oleos essenciais e apos 24 horas de incubacao fez-se a verificacao de celulas viaveis atraves do metodo MTT. Os oleos essenciais que apresentaram melhores atividade tripanocida foram os das folhas Kielmeyera coriacea (IC50 6,4 µg mL-1 ) e frutos Xylopia aromatica (IC50 6,4 µg mL-1 ), seguidos pelo oleo dos frutos Zanthoxylum xvi rhoifolium (IC50 8,1 µg mL-1 ).Os oleos essenciais da folhas Zanthoxylum riedelianum (IC50 13,1 µg mL-1 ), folhas Zanthoxylum rhoifolium (IC50 29,5 µg mL-1 ) tambem apresentaram otima atividade mesmo possuindo valores de concentracoes inibitorias mais elevadas quando comparados com o controle positivo benzonidazol (IC50 9,8 µg mL-1 ). Todos os oleos essenciais apresentaram toxicidade contra celulas LLCMK2 em concentracoes maiores que 100 µg mL-1 , sendo assim considerados de baixa citotoxidade. Desta forma podemos considerar todos os oleos essenciais excelentes candidatos para investigacao de nova droga antiparasitaria.

Lipoxygenase (LOX) plays an important role in inflammatory processes and Arrabidaea brachypoda (DC.) Bureau (Bignoniaceae) has been described as presenting anti-inflammatory activity. Therefore, the objective of this study was to develop a high-performance liquid chromatography (HPLC) procedure to directly recognize LOX inhibitor compounds in A. brachypoda crude extract, facilitating the isolation, characterization of bioactive compounds, evaluation of natural compounds using an in vitro 15-LOX assay and prediction of the most probable binding modes of their main constituent through molecular docking simulations. The chemical analysis was performed by ethanol crude extract microfractionation using HPLC-DAD (diode array detector) associated to a fraction collector. The bioactive chromatogram displayed a peak with 50.9% LOX inhibition at 13.6 min retention time. The extract was purified and conandroside was isolated, presenting a LOX inhibitory activity with an inhibitory concentration (IC50) of 7.8 ± 1.1 µM, close to standard quercetin (IC50 7.6 ± 0.3 µM). Additionally, conandroside was not cytotoxic to normal cells (GM07492A). The LOX-conandroside complex displayed a slightly higher docking score (92.7) than quercetin (71.5). These results together suggest that conandroside could be explored as lipoxygenase inhibitor.

Fridericia speciosa (Bignoniaceae) is a liana that occurs in humid to dry vegetation in eastern and southeastern Brazil. Species belonging to the genus Fridericia are employed as medicinal plants. This study evaluates the antipromastigote and cytotoxic activities of the crude extract, fractions, and compounds isolated from F. speciosa, and an HPLC (High-Performance Liquid Chromatography) analytical method was used to quantify the bioactive flavonoids. The flavonoids alpinetin (1), luteolin (2), diosmetin (3), and apigenin (4) were isolated from the active EtOAc-soluble fraction (EAF) of the crude ethanol extract (LCE) obtained from F. speciosa leaves. Both LCE and EAF were active against the normal human lung fibroblast cell line GM07492A (IC50 of 460.7 µg mL-1 and 381.4 µg mL-1, respectively). Only EAF showed activity against Leishmania amazonensis (80.4% at 50 µg mL-1). Compounds 1 and 2 were quantified by HPLC-DAD in both LCE (1: 6.21%; 2: 1.11%) and EAF (1: 45.32%; 2: 2.00%). At 100 µM, compounds1-4 inhibited L. amazonensis flagellar motility by 40.2%, 26.8%, 1.0%, and 24.8%, respectively, while their toxicities (IC50) to the normal cell were > 1000, 353.0, 766.2, and >1000 µg mL-1, respectively. Therefore, F. speciosa leaves are a prolific source of bioactive flavonoids.

Context: (−)-6,6′-Dinitrohinokinin (DNHK) display remarkable antiparasitic activity and was, therefore, incorporated into a nanoparticle formulation. Objective: Incorporation of DNHK in poly lactic-co-glycolic acid (PLGA) nanoparticles aiming to improve its biological activities. Materials and methods: Synthesis, characterization and incorporation of DNHK into glycolic acid (PLGA) nanoparticles by nanoprecipitation method. The nanoparticles were characterized by ultraviolet-visible spectroscopy, X-ray diffraction, field emission electron microscopic scanning mansoni (FESEM), and dynamic light scattering (DLS). For the in vitro test with Schistosoma mansoni, the DNHK-loaded PLGA was diluted into the medium, and added at concentrations 10–200 µM to the culture medium containing one adult worm pair. The parasites were kept for 120 h and monitored every 24 h to evaluate their general condition, including: pairing, alterations in motor activity and mortality. Results: The loaded PLGA nanoparticles gave an encapsulation efficiency of 42.2% and showed spherical characteristics in monodisperse polymeric matrix. The adult worm pairs were separated after 120 h of incubation for concentrations higher than 50 µM of DNHK-loaded PLGA. The groups incubated with 150 and 200 µM of DNHK-loaded PLGA for 24 and 120 h killed 100% of adult worms, afforded LC50 values of 137.0 ± 2.12 µM and 79.01 ± 1.90 µM, respectively, which was similar to the effect displayed by 10 µM of praziquantel. Discussion and conclusions: The incorporation of DNHK-loaded showed schistosomicidal activity and allowed its sustained release. The loaded PLGA system can be administered intravenously, as well as it may be internalized by endocytosis by the target organisms.

Copaifera species folkloric names are "copaíbas, copaibeiras, copaívas or oil stick", which are widely used in Brazilian folk medicine. Among all ethnopharmacological applications described for Copaifera spp oleoresins, their anti-inflammatory effect stands out. However, the knowledge of anti-inflammatory and antinociceptive properties of Copaifera pubiflora Benth is scarce.To investigate the cytotoxic, anti-inflammatory, and antinociceptive activities of C. pubiflora oleoresin (CPO), and its major compound ent-hardwickiic acid (HA).The phosphatase assay was used to evaluate the cytotoxicity of CPO and HA in three different cell lines. CPO and HA doses of 1, 3, and 10 mg/kg were employed in the biological assays. The assessment of motor activity was performed using open-field and rotarod tests. Anti-inflammatory activity of CPO and HA was assessed through luciferase assay, measurement of INF-γ, IL-1β, IL-6, IL-10, and TNF-α in a multi-spot system with the immortalized cell line THP-1, zymosan-induced arthritis, and carrageenan-induced paw edema. Acetic acid-induced abdominal writhing and formalin tests were undertaken to evaluate the antinociceptive potential of CPO and HA. In addition, the evaluation using carrageenan was performed to investigate the effect of CPO in pain intensity to a mechanical stimulus (mechanical hyperalgesia), using the von Frey filaments. A tail-flick test was used to evaluate possible central CPO and HA actions.In the cytotoxicity evaluation, CPO and HA were not cytotoxic to the cell lines tested. CPO and HA (10 mg/kg) did not affect animals' locomotor capacity in both open-field and rotarod tests. In the luciferase assay, CPO and HA significantly reduced luciferase activity (p 0.05). This reduction indicates a decrease in NF-κB activity. HA and CPO decreased INF-γ, IL-1β, IL-6, IL-10, and TNF-α at 24 and 72 h in the multi-spot system. In zymosan-induced arthritis, CPO and HA decreased the number of neutrophils in the joint of arthritic mice and the number of total leukocytes (p 0.05). In experimental arthritis HA significantly decreased joint swelling (p 0.05). CPO and HA also increased the mechanical threshold during experimental arthritis. HA and CPO significantly inhibited the carrageenan-induced paw edema, being the doses of 10 mg/kg the most effective, registering maximum inhibitions of 58 ± 8% and 76 ± 6% respectively, p 0.05. CPO and HA reduced the nociceptive behavior in both phases of formalin at all tested doses. The highest doses tested displayed inhibitions of 87 ± 1% and 72 ± 4%, respectively, p 0.001, in the first phase, and 87 ± 1% and 81 ± 2%, respectively, p 0.001, in the second phase. Oral treatment of CPO and HA (1, 3, 10 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhings, and the 10 mg/kg dose was the most effective with maximum inhibitions of 86 ± 2% and 82 ± 1%, respectively, p 0.001. Both HA and CPO significantly decreased the intensity of mechanical inflammatory hyper-nociception on carrageenan-induced hyperalgesia at all tested doses, and 10 mg/kg was the most effective dose with maximum inhibitions of 73 ± 5% and 74 ± 7%, respectively, p 0.05.CPO increased the tail-flick latencies in mice, and concomitant administration of naloxone partially reduced its effect.CPO and HA may inhibit the production of inflammatory cytokines by suppressing the NF-κB signaling pathway, resulting in anti-inflammatory and antinociceptive activities.

The biotransformation of the lignan (-)-cubebin by filamentous fungi Aspergillus terreus and Aspergillus niger is an efficient bioprocess for obtaining (-)-hinokinin and (-)-parabenzlactone. The relevance of getting (-)-hinokinin is due to its promising effect against oral pathogens, especially S. sanguinis (both MIC and MBC 12.5 μg/mL), and other previous reported effects against Chagas disease and as anti-inflammatory. The advantage of using fungal transformation is the use of non-toxic and/or non-pollutant reagents and/or solvents in comparison with semi-synthesis. Microbial transformation of (-)-cubebin is also important to evaluate its human metabolism, since Aspergillus species are capable of mimicking P450 reactions, providing possible products of the metabolism, which is important in the assessment of its efficacy and safety. Furthermore, the present study describes a reliable RP-HPLC method to perform quantification of (-)-hinokinin in fungal extracts. It is simple, fast, selective, linear, precise, accurate and robust according to validation guidelines.

Made available in DSpace on 2018-12-11T16:45:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (−)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (−)-hinokinin (HK) and (−)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween� 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 – cyclooxygenase-2) interaction in comparison with CUB and HK. N�cleo de Pesquisas em Ci�ncias Exatas e Tecnol�gicas Universidade de Franca, Av. Dr. Armando Salles Oliveira 201 School of Pharmaceutical Sciences of Ribeir�o Preto University of S�o Paulo, Av. do Caf� S/N Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista J�lio de Mesquita Filho (UNESP), Av Brasil 56 Programa de P�s-Gradua��o em Ci�ncia Animal Universidade de Franca, Av. Dr. Armando Salles Oliveira 201 Departamento de Quı́mica Universidade Federal de Santa Catarina, Campus Universit�rio Trindade, CP 476 Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista J�lio de Mesquita Filho (UNESP), Av Brasil 56 FAPESP: 2005/00494-7 FAPESP: 2011/07623-8 CNPq: 303349/2013-1 CNPq: 88881.068346/2014-01

RESUMO: Dois experimentos foram realizados com o objetivo de avaliar o uso das sementes secas de Piper cubeba nas dietas de frangos de corte de 1 a 21 dias de idades e seus efeitos sobre o perfil bioquímicos do sangue e na biometria dos órgãos das aves. Em cada experimento 240 pintos de corte machos, com um dia de idade da linhagem Cobb foram distribuídos em um delineamento inteiramente casualizado, com cinco tratamentos e quatro repetições de 12 aves por parcela experimental. No primeiro experimento foi avaliado o uso da Piper cubeba em dietas consideradas de alta digestibilidade, a base de milho e farelo de soja, e no segundo avaliou-se o uso da pimenta em dietas de baixa digestibilidade, as quais foram obtidas com a inclusão de farinha de carne e ossos. Com relação aos dados de perfil bioquímico sanguíneo do experimento I, com exceção da gama glutamil transferase, todos os demais níveis séricos se apresentaram dentro dos limites recomendados para aves, e apenas os níveis de triglicerídeos diferiram entre os tratamentos (P0,05) para a biometria dos órgãos. Nas condições em que os experimentos foram realizados a inclusão das sementes de Piper cubeba na ração para frangos de corte não proporcionou alterações bioquímicas e biométricas que possam limitar seu uso como material vegetal para os estudos fitogênicos. ABSTRACT: Two experiments were conducted to evaluate the use of dried seeds of Piper cubeba in the diets of 1 to 21-day-old broilers and its effect on biochemical blood profile and biometry of the organs. In each experiment, 240 one-day-old male broiler chicks Cobb were distributed in a completely randomized design with five treatments and four replicates of 12 birds per experimental plot. The first experiment evaluated the use of Piper cubeba in considered highly digestible diets based on corn and soybean meal, and the second evaluated the use of pepper in low digestibility diets, which were obtained with the inclusion of meat and bone meal. Regarding the blood chemistry profile data of the experiment I, with the exception of gamma glutamyl transferase, all other serum levels were within recommended limits for poultry, and only triglyceride levels differed between treatments (P 0.05) for the biometry of organs. The conditions under which the experiments were performed at inclusion of Piper cubeba seeds in feed for broilers has not provided any toxicity to poultry.

The occurrence of sulfated steroids and phenolics in marine organisms is quite widespread, being typically reported from Echinoderms. In contrast, alkane and alkene aliphatic sulfates are considerably rarer with examples being reported from a diverse array of organisms including echinoderms, sponges and ascidians. While no ecological roles for these metabolites have been proposed, they do exhibit a diverse array of biological activities including thrombin inhibition; the ability to induce metamorphosis in larvae; antiproliferative, antibacterial and antifungal properties; and metalloproteinase inhibition. Of particular interest and an avenue for future development is the finding of antifouling properties with low or nontoxic effects to the environment. This review focuses on alkyl sulfates and related sulfamates, their structures and biological activities. Spectroscopic and spectrometric techniques that can be used to recognize the presence of sulfate groups are also discussed, data for which will enhance the ability of researchers to recognize this class of chemically- and biologically-interesting marine natural products.

Made available in DSpace on 2020-12-10T19:43:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) This study describes the in vitro anthelmintic activity of a hydroalcoholic extract from the fruit of Piper cubeba and its major isolated components against the eggs and larvae of gastrointestinal nematodes obtained from naturally-infected ovines. In vitro anthelmintic activity was evaluated using the egg hatch test (EHT), larval development test (LDT) and L3 migration inhibition test (LMT). The extract showed ovicidal and larvicidal activity, with an EC50 of 200 mu g/mL and 83.00 mu g/mL in the EHT and LDT, respectively. The extract inhibited 100% of larval migration at the lowest tested concentration (95 mu g/mL). The crude extract was purified using successive silica gel chromatographic columns, which revealed the lignans hinokinin, cubebin and dihydrocubebin as the major compounds that were present, which were then used in in vitro tests. Cubebin, dihydrocubebin and hinokinin showed higher activity than the crude extract, with an EC50 for ovicidal activity of 150.00 mu g/mL, 186.70 mu g/mL and 68.38 mu g/mL, respectively. In the LDT, cubebin presented an EC50 of 14.89 mu g/mL and dihydrocubebin of 30.75 mu g/mL. Hinokinin inhibited 100% the larval development at all concentrations evaluated. In the LMT, dihydrocubebin inhibited 100% the larval migration in all concentrations evaluated while cubebin and hinokinin showed EC50 values of 0.89 mu g/mL and 0.34 mu g/mL, respectively. P. cubeba extract is rich in several classes of active compounds, but here we demonstrate that the described anthelmintic activity may be related to the presence of these lignans, which are present in larger concentrations than other components of the extract. Our results demonstrate for first time the anthelmintic activity against gastrointestinal nematodes in sheep for this class of special metabolites that are present in P. cubeba fruit. However, future detailed studies are needed to evaluate the effectiveness of P. cubeba fruits extract and active lignans in in vivo tests. Univ Estadual Paulista, Fac Engn IIha Solteira, Dept Fis & Quim, Av Brasil 56, BR-15385000 Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Engn IIha Solteira, Dept Biol & Zootecnia, Rua Moncao 226, BR-15385000 Sao Paulo, SP, Brazil Univ Franca, Nucleo Pesquisa Ciencias Exatas & Tecnol, Av Salesde Oliveira 201,Parque Univ, BR-14404600 Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Engn IIha Solteira, Dept Fis & Quim, Av Brasil 56, BR-15385000 Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Engn IIha Solteira, Dept Biol & Zootecnia, Rua Moncao 226, BR-15385000 Sao Paulo, SP, Brazil FAPESP: 2016/17270-9

EnglishHyptis marrubioides (Lamiaceae) is a medicinal plant that is native from Brazilian Cerrado. In vitro propagation techniques make use of elicitors to alter metabolic pathways, affecting how molecules are produced both qualitatively and quantitatively. This research aimed to evaluate how abiotic elicitors salicylic acid (SA) and silver nitrate (SN) at concentrations of 30µM or 60µM influence Hyptis marrubioides seedling growth by two different in vitro culture methods. The rutin content was quantified by HPLC-DAD. Compared to an untreated culture, the H. marrubioides methanolic extracts cultured in MS medium for 10 days followed by culture in MS medium containing SN (30µM) for 20 days had 1.28 times higher rutin content. In a second experiment, seedlings were cultured in MS medium for 20 days, and then the desired elicitor was added to the culture and allowed to remain in contact with the medium for three and six days. SA (30µM) gave the best results: rutin production was 16.56-foldhigher than the control after six days. SN (30µM) increased the rutin content by 1.17-fold. At the two concentrations evaluated during the elicitation experiments, neither SA nor SN altered the growth parameters shoot length, leaf number, and fresh and dry weight of H. marrubioides seedlings grown in vitro as compared to the control. Based on these results, the abiotic elicitors SA and SN successfully provide Hyptis marrubioides with increased rutin content in vitro. Key words: salicylic acid; HPLC-DAD; tissue culture; silver nitrate; elicitation; plant growth regulators portuguesHyptis marrubioides (Lamiaceae) e uma planta medicinal nativa do Cerrado brasileiro. Tecnicas de propagacao in vitro fazem uso de elicitores para alterar as vias metabolicas, afetando a producao de moleculas qualitativa e quantitativamente. Este trabalho teve como objetivo avaliar como os elicitores abioticos acido salicilico (SA) e nitrato de prata (SN) nas concentracoes de 30µM ou 60µM influenciam no crescimento de plântulas de Hyptis marrubioides por dois diferentes metodos de cultivo in vitro. O teor de rutina foi quantificado por CLAE-DAD. Em comparacao com uma cultura nao tratada, os extratos metanolicos de H. marrubioides cultivados em meio MS por 10 dias, seguidos de cultura em meio MS contendo SN (30µM) por 20 dias, apresentaram 1,28 vezes maior teor de rutina. Em um segundo experimento, as plântulas foram cultivadas em meio MS por 20 dias, e entao o elicitor desejado foi adicionado a cultura e deixado em contato com o meio por tres e seis dias. SA (30µM) forneceu os melhores resultados na producao de rutina, sendo 16,56 vezes maior do que o controle apos seis dias. SN (30µM) aumentou o teor de rutina em 1,17 vezes. Nas duas concentracoes avaliadas durante os experimentos de elicitacao, nem SA nem SN alteraram os parâmetros de crescimento, como comprimento da parte aerea, numero de folhas ou peso fresco e seco das plântulas de H. marrubioides cultivadas in vitro em relacao ao controle. Com base nestes resultados, os elicitores abioticos SA e SN forneceram com sucesso Hyptis marrubioides in vitro com maior conteudo de rutina. Palavras-chave: acido salicilico; CLAE-DAD; cultura de tecidos; elicitacao; nitrato de prata; reguladores de crescimento vegetal

Recent publications have highlighted the numerous biological activities attributed to the lignan (−)-cubebin (1), Piper cubeba L. f., Piperaceae, and ongoing studies have focused on its structural optimization, in order to obtain derivatives with greater pharmacological potential. The aim of this study was the obtainment of (1), its semisynthetic derivatives and evaluation of antibacterial activity. The extract of the seeds of P. cubeba was chromatographed, subjected to recrystallization and was analyzed by HPLC and spectrometric techniques. It was used for the synthesis of: (−)-O-methylcubebin (2), (−)-O-benzylcubebin (3), (−)-O-acetylcubebin (4), (−)-O-(N,N-dimethylamino-ethyl)-cubebin (5), (−)-hinokinin (6) and (−)-6.6′-dinitrohinokinin (7). The evaluation of the antibacterial activity has been done by broth microdilution technique for determination of the minimum inhibitory concentration and the minimum bactericidal concentration against Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces naeslundii, Bacteroides fragilis and Fusobacterium nucleatum. It was possible to make an analysis regarding the relationship between structure and antimicrobial activity of derivatives against microorganisms that cause endodontic infections. The most promising were minimum inhibitory concentration =50 μg/ml against P. gingivalis by (2) and (3), and minimum inhibitory concentration =100 μg/ml against B. fragilis by (6). Cytotoxicity assays demonstrated that (1) and its derivatives do not display toxicity. Keywords: Lignans, Piper cubeba, (−)-cubebin, Semisynthetic derivatives, Antibacterial activity

Made available in DSpace on 2022-04-28T19:03:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-05-01 Schistosomiasis, a chronic disease that affects million people worldwide, is caused by trematodeflukes of the genus Schistosoma. The lack of an anti-schistosomiasis vaccine and massive monother-apy with praziquantel reinforces the need for search and development of new therapeutic drugs.Recently, we demonstrated that the essential oil of Piper cubeba L., Piperaceae, and their derivative diben-zylbutyrolactolic (−)-6,6′-dinitrohinokinin, presents in vitro and in vivo activities against Schistosomamansoni. Here, we identified changes in the protein expression after exposure to dibenzylbutyrolac-tolic (−)-6,6′-dinitrohinokinin. We applied two-dimensional gel electrophoresis (2-DE) to S. mansonisoluble protein extracts and observed at least 38 spots to be affected by dibenzylbutyrolactolic (−)-6,6′-dinitrohinokinin. We further identified 25 differentially expressed proteins by mass spectrometry.Enrichment for biological processes and predictive analyses of protein-protein interactions suggest thatdibenzylbutyrolactolic (−)-6,6′-dinitrohinokinin targets proteins involved mainly in metabolic processes,especially carbohydrate metabolism. In summary, this study provides an interesting approach to under-stand the anti-parasitic activity of semi-synthetic (−)-6,6′-dinitrohinokinin a derivative compound fromlignan and for the development of new therapy strategies. Grupo de Pesquisa em Ciências Exatas e Tecnológicas Universidade de Franca Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo Instituto de Genética e Bioquímica Universidade Federal de Uberlândia Faculdade de Engenharia Universidade do Estado de São Paulo Faculdade de Ciências Farmacêuticas Universidade de São Paulo Faculdade de Ciências Farmacêuticas Universidade de Juiz de Fora

Zanthoxylum naranjillo and Z. tingoassuiba (Rutaceae) are traditional herbal medicines with various biological activities including anti-inflammatory, analgesic, and antimalarial action. In this work, we have developed a simple HPLC-DAD method to quantify sesamin, a bioactive lignan present in Z. naranjillo and Z. tingoassuiba; egonol was the internal standard. According to the developed method, 11.07 ± 1.66, 8.69 ± 0.95, and 15.11 ± 0.72 µg/mL sesamin was present in the ethanol extract of Z. naranjillo leaves, in the methanol extract of Z. naranjillo leaves, and in the methanol extract of Z. tingoassuiba bark, respectively. The limits of detection and quantification were 0.32 and 1.06 µg/mL, respectively. The developed method can be easily applied during routine analysis of sesamin in these medicinal plants.

Miconia albicans (Sw.) Triana and Miconia chamissois Naudin, commonly known as “pixirica” and “pixirica-acu”, two Melastomataceae species, are commonly found in Cerrado areas. M. albicans species grows in dry and humid habitats, so it has adapted to both conditions and M. chamissois species grows in humid environment only. In this work, we have investigated the content of triterpenes, flavonols and flavanones in three different Cerrado fragments of Sao Paulo State, involving distinct environments (dry and humid) and seasons (dry and rainy) to comprehend the complex interactions among plants and the seasonal, environmental conditions and geographic locations. The leaves plants materials were harvest in August 2016 (dry season) and November/December 2016 (rainy season) in Pirassununga, Pedregulho and Luiz Antonio in dry and humid environments. The contents of the standards rutin (R), quercetin (Q), miconioside B (B), matteucinol 7-O-β-apiofuranosyl(1 → 6)-β-glucopyranoside (matt), ursolic acid (AU), and oleanolic acid (AO) were determined by HPLC-DAD. The data were analyzed using nonparametric tests, Pearson's linear correlation, principal component analysis and hierarchical cluster analysis. The results demonstrated similar flavanone and triterpene production during the dry period, and similar flavonol and flavanone production in the rainy season, thus confirming a seasonal variation in the content of the compounds in the evaluated specimens. Our results also demonstrated intra- and inter-population variations in compounds patterns, M. albicans contained major amounts of the flavonols R and Q; their concentrations were higher in the rainy season. B and matt were the major compounds in M. chamissois; the matt concentration decreased in the rainy season. The triterpenes AU and AO occurred in both M. albicans and M. chamissois, but their production dropped during the rainy periods. Thus corroborating the adaptation of M. albicans and M. chamissonis to the high stress and low levels of resources presented in Cerrado.

Made available in DSpace on 2020-12-10T19:55:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) This paper reports the synthesis of (+/-)-licarin A 1, a dihydrobenzofuran neolignan, resultant of an oxidative coupling reaction of isoeugenol and horseradish peroxidase (HRP) enzyme. Following, three semi-synthetic derivatives from this compound were obtained: benzylated (+/-)-licarin A 2, methylated (+/-)-licarin A 3 and acetylated (+/-)-licarin A 4. After structural elucidation and assignment by Nuclear Magnetic Resonance of H-1, C-13 and DEPT, all compounds were evaluated in vitro against Trypomastigote forms of Trypanosoma cruzi (T. cruzi), the etiologic agent of Chagas disease, and Schistosoma mansoni (S. mansoni) worms, the etiologic agent of schistosomiasis. Compound (4) was the most active against S. mansoni adult worms, displaying worm viability reduction at 25 mu M and mortality of all worms at 100 and 200 mu M within 24 h. Compound 1 was the second most active, showing worm viability reduction at 50 mu M and mortality of 25% and 100% of worms in 24h at concentrations of 100 and 200 mu M, respectively. In addition, theoretical calculations aiming at finding molecular properties that showed the correlation for schistosomicidal and trypanocidal activities of (+/-)-licarin A and three of its semi-synthetic derivatives were also performed. Univ Franca, Nucleo Ciencias Exatas & Tecnol, Grp Pesquisa Produtos Nat, Ave Dr Armando Salles de Oliveira 201, BR-14404600 Franca, SP, Brazil Univ Sao Paulo, Escola Ciencias Farmaceut Ribeirao Preto, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP, Brazil Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA Univ Mississippi, Sch Pharm, Res Inst Pharmaceut Sci, Natl Ctr Nat Prod Res, University, MS 38677 USA Univ Estadual Paulista, Fac Engn, Dept Fis & Quim, Ilha Solteira, SP, Brazil IF Suldeminas, Ave Maria da Conceicao Santos,900 Parque Real, BR-37550000 Pouso Alegre, MG, Brazil Univ Estadual Paulista, Fac Engn, Dept Fis & Quim, Ilha Solteira, SP, Brazil FAPESP: 1998/14956-7 FAPESP: 2009/05049-2 FAPESP: 2011/07623-8 FAPESP: 2017/24856-2

Encouraged by the anti-inflammatory activity of hinokinin in vivo, which is also observed for the analogues dinitrohinokinin and diidrocubebin, herein we used in vitro and in silico methods to assess their selectivity profiles and predict their binding modes with Cyclooxygenases (COX-1 and 2). The in vitro assays demonstrated dinitrohinokinin is about 13 times more selective for COX-2 than for COX-1, a similar profile observed for the drugs celecoxib (selective index ≈9) and meloxicam (selective index ≈11). Predictions of the binding modes suggested dinitrohinokinin interacts with COX-2 very similarly to rofecoxib, exploring residues at the hydrophilic pocket of the enzyme that accessible to ligands only in this isoform. This lignan also interacts with COX-1 in a similar mode to meloxicam, blocking the access of the substrate to the catalytic cleft. Therefore, dinitrohinokinin is a promising lead for the design of selective COX-2 inhibitors.

This work evaluated the in vitro inhibitory activity of the crude ethanolic extract from the aerial parts of Cuspidaria pulchra (Cham.) L.G. Lohmann against 15-lipoxygenase (15-LOX). The bioassay-guided fractionation of the n-butanol fraction, which displayed the highest activity, led to the isolation of three compounds: caffeoylcalleryanin (1), verbascoside (2) and 6-hydroxyluteolin-7-O-β-glucoside (3). Assessment of the ability of the isolated compounds to inhibit 15-LOX revealed that compounds 1, 2 and 3 exerted strong 15-LOX inhibitory activity; IC50 values were 1.59, 1.76 and 2.35 μM respectively. The XTT assay showed that none of the isolated compounds seemed to be significantly toxic.

According to Schneider (1984: 4, 119-120), anthropological studies of kinship are anchored in a Doctrine of the Genealogical Unity of Mankind which has distorted ethnographic perception and consecrated a non-subject. This Doctrine can be summarized as follows: in all human cultures kinship concerns the acknowledgement of natural ties among individuals, thus warranting its universal translation in genealogical terms. This article counters Schneider’s criticism on two fronts: inquiring if the genealogical method should necessarily be understood as a means of translation; and challenging whether the definition of the genealogical method requires such a Doctrine in the first place. In parallel, drawing considerations from ethnographic research concerning the Enawene-Nawe, this article, within the horizon of the alliance theory, argues in favor of the rehabilitation of the genealogical method, which in the present century cannot dismiss computational tools. This, considering that “the first task of anthropology, prerequisite to all others, is to understand and formulate the symbols and meanings and their configuration, that a particular culture consists of” (Schneider 1984: 196, emphasis in the original). Para Schneider, os estudos antropológicos de parentesco estão ancorados em uma Doutrina da Unidade Genealógica da Humanidade que teria distorcido a percepção etnográfica e consagrado um “non-subject”. Esta Doutrina pode ser assim resumida: em todas as culturas humanas, parentesco tem a ver com o reconhecimento de vínculos naturais entre os indivíduos, assim afiançando sua tradução universal em termos genealógicos. Este artigo se contrapõe à crítica de Schneider em duas frentes: indaga se necessariamente convém entender o método genealógico como um dispositivo de tradução; em outra, questiona se o método genealógico requer tal Doutrina para se definir. Paralelamente, a partir da pesquisa etnográfica concernente aos Enawene-Nawe, este artigo, nos horizontes da teoria da aliança, argumenta em favor da reabilitação do método genealógico que, neste século, não pode abrir mão de ferramentas computacionais. Isto, considerando que “a primeira tarefa da antropologia, pré-requisito de todas as outras, é entender e formular os símbolos e sentidos e suas configurações, de que uma cultura particular consiste” (ênfase no original, Schneider, 1984: 196).

Vochysia divergens (Vochysiaceae) is considered an invasive species in the wetlands of the Brazilian Pantanal, which hinders the cultivation of agricultural species. In this study, we evaluated the chemical profile by HPLC-DAD (high-performance liquid chromatography-diode array detector) of leaves extracts from V. divergens seedlings inoculated with endophytic fungi isolated from V. divergens roots. These fungi were collected on dry (D) and wet (W) seasons in the Pantanal. The presence of tannin hexahydroxydiphenoyl (HHDP)-galloyl-glucose and flavone 3',5'-dimethoxy-luteolin were predominant in the seedlings inoculated with endophytic fungi W experiments at 100 and 80%, respectively. Likewise, flavone 3',5-dimethoxy-luteolin-7-O-β-glucoside showed a similar representation in the two evaluated periods, compared with 5-methoxy-luteolin, which was detected only in seedlings inoculated with W endophytic fungi. This approach is new to V. divergens, which has no scientific data on its in vitro elicitation, in the search for a better understanding of the ecological relationships of this species.

This paper reports on the in vitro activity of the hydroalcoholic extract of P. glomerata roots, its hydrolyzed fractions, and pfaffic acid against Trypanosoma cruzi. The hydroalcoholic extract obtained from dried, milled P. glomerata roots was submitted to acid hydrolysis followed by partition with chloroform. The concentrated chloroform fraction was suspended in MeOH/H2O and partitioned with hexane (F1), chloroform (F2), and ethyl acetate (F3), in this sequence. The trypanocidal activity of the hydrolyzed extract and its fractions was evaluated in vitro. The hydroalcoholic extract displayed low activity, but fraction F1 was active against trypomastigotes of the Y strain of T. cruzi, with IC50 = 47.89 μg/mL. The steroids campesterol (7.7%), stigmasterol (18.7%), β-sitosterol (16.8%), Δ-7-estigmastenol (4.6%), and Δ-7-epinasterol (7.5%) were the major constituents of F1, along with fatty acid esters (7.6%) and eight aliphatic hydrocarbons (30.1%). Fractions F2 and F3 exhibited moderate activity, and pfaffic acid, one of the main chemical constituents of these fractions, displayed IC50 = 44.78 μM (21.06 μg/mL). On the other hand, the hydroalcoholic extract of P. glomerata roots, which is rich in pfaffosides, was inactive. Therefore, the main aglycone of pfaffosides, pfaffic acid, is much more active against trypomastigotes of the Y strain of T. cruzi than its corresponding glycosides and should be further investigated. This article is protected by copyright. All rights reserved.

Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral data of these compounds is also presented.

The schistosomicidal and cytotoxic activities of norneolignans isolated from Styrax pohlii are used to relieve fever. The norneolignans homoegonol [2] and homoegonol glucoside [4] provided the best results against S. mansoni adult worms. At 200 μM, compounds 2 and 4 killed 25% and 50% of the parasites in 120 h, while egonol [1], homoegonol gentiobioside [3], and egonol gentiobioside [5] reduced their motor activity to 12.5%, 12.5%, and 37.5% in 120 h, respectively. With respect to the cytotoxic activity, the IC50 values were greater than 800 μM for 1, 5, and 3 and 192.5 and 253.1 μM for 2 and 4, respectively.