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5-Hydroxymethylfurfural (5-HMF) is a renewable platform chemical used as a source for obtaining diverse fine chemicals. In this letter, we report the synthesis of 5-HMF-based oxazole compounds. While 5-HMF could be easily converted into the oxazole derivative through the Van Leusen reaction, the direct arylation step needed to access the final compounds was problematic at first. After optimization, a palladium-catalyzed procedure has been developed and used for the synthesis of a series of 33 derivatives. This article reports an extension of the late-stage CH arylation reaction as an application to the oxazole platform derived from biosourced 5-HMF. The challenges in the preparation of the derivatives containing some electron-withdrawing substituents were overcome by the use of a palladium-free method.

Chemical scaffolds of natural products have historically been sources of inspiration for the development of novel molecules of biological relevance, including hit and lead compounds. To identify new compounds active against Trypanosoma cruzi, we designed and synthesized 46 synthetic derivatives based on the structure of two classes of natural products: tetrahydrofuran lignans (Series 1) and oxazole alkaloids (Series 2). Compounds were screened in vitro using a cellular model of T. cruzi infection. In the first series of compounds, 11 derivatives of hit compound 5 (EC50 = 1.1 µM) were found to be active; the most potent (7, 8, and 13) had EC50 values of 5.1–34.2 µM. In the second series, 17 analogs were found active at 50 µM; the most potent compounds (47, 49, 59, and 63) showed EC50 values of 24.2–49.1 µM. Active compounds were assessed for selectivity, hemocompatibility, synergistic potential, effects on mitochondrial membrane potential, and inhibitory effect on trypanothione reductase. All active compounds showed low toxicity against uninfected THP-1 cells and human erythrocytes. The potency of compounds 5 and 8 increased steadily in combination with benznidazole, indicating a synergistic effect. Furthermore, compounds 8, 47, 49, 59, and 63 inhibited parasitic mitochondria in a dose-dependent manner. Although increased reactive oxygen species levels might be involved in the mitochondrial effects caused by compounds, the results indicate that the mechanism of action is not dependent on trypanothione reductase inhibition. In silico calculation of chemical descriptors and principal component analysis showed that the active compounds share common chemical features with other trypanocidal molecules and are predicted to have a good ADMET profile. Overall, the results suggest that the compounds are important candidates to be further studied for their potential against T. cruzi.

Secondary metabolites obtained from natural sources are medicinally relevant molecules. About one-third of all FDA-approved drugs are derived from or based on natural products, which suggests that molecular optimization is often required for translation from benchtop to clinical practice. Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease highly prevalent in Latin America. It has a significant impact on socioeconomic indicators and is not easily cured by the two currently available drugs, benznidazole and nifurtimox. Considering the importance of developing new bioactive molecules based on natural products, this article reviews 21 years of literature reports on the semisynthesis and total synthesis of new compounds targeting T. cruzi. From 1997 to 2018, sixty-six articles reporting five hundred and thirty-seven molecules active against different strains and life stages of the parasite were published. Quinones, alkaloids, terpenes, and lignans were the four largest classes of derivatives, the majority of which had IC50 values low enough to indicate that natural product derivatives can be an important source of potential new drugs to treat Chagas disease. We highlight important molecules in each secondary metabolite class, discussing factors such as selectivity and the basis for their design. An assessment of drug-likeness parameters was performed, which might prove useful for selecting lead compounds for preclinical drug studies.

Despite the impressive scientific and technological advances of recent decades, no effective treatment is currently available for Chagas disease. Our research group has been studying the design and synthesis of analogues of natural lignans aiming to identify compounds with antiparasitic activity. This article reports the synthesis of 42 novel bis-heterocyclic derivatives and the structure-activity relationship study conducted based on results of biological assays against Trypanosoma cruzi amastigotes. Thirty-seven compounds were active, and eight of them had GI50 values lower than 100 μM (GI50 88.4–12.2 μM). A qualitative structure activity relationship study using three dimensional descriptors was carried out and showed a correlation between growth inhibitory potency and the presence of bulky hydrophobic groups located at rings A and D of the compounds. Compound 3-(3,4-dimethoxyphenyl)-5-((4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)methyl)isoxazole (31) was the most active in the series (GI50 12.2 μM), showing, in vitro, low toxicity and potency similar to benznidazole (GI50 10.2 μM). These results suggest that this compound can be a promising scaffold for the design of new trypanocidal compounds.

This paper reports the in vitro antiproliferative effects, antiprotozoal, anti-herpes and antimicrobial activities of 32 organic extracts of 14 marine sponges and 14 corals collected in northeast Brazilian coast. The ethanolic extracts of the sponges Amphimedon compressa and Tedania ignis, and the acetone extract of Dysidea sp. showed relevant results concerning the antiproliferative effects against A549, HCT-8, and PC-3 cell lines by sulforhodamine B assay, but also low specificity. Concerning the antiprotozoal screening, the ethanolic extract of Amphimedon compressa and the acetone and ethanolic extracts of Dysidea sp. were the most active against Leishmania amazonensis and Trypanosoma cruzi expressing β-galactosidase in THP-1 cells. In the preliminary anti-HSV-1 (KOS strain) screening, the ethanolic extracts of the sponges Amphimedon compressa, Haliclona sp. and Chondrosia collectrix inhibited viral replication by more than 50%. The most promising anti-herpes results were observed for the ethanolic extract of Haliclona sp. showing high selective indices against HSV-1, KOS and 29R strains (SI> 50 and >79, respectively), and HSV-2, 333 strain (IS>108). The results of the antibacterial screening indicated that only the ethanolic extract of Amphimedon compressa exhibited a weak activity against Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli by the disk diffusion method. In view of these results, the extracts of Amphimedon compressa, Tedania ignis and Dysidea sp. were selected for further studies aiming the isolation and identification of the bioactive compounds with antiproliferative and/or antiprotozoal activities. The relevant anti-herpes activity of the ethanolic extract of Haliclona sp. also deserves special attention, and will be further investigated. Resumo Este artigo reporta as atividades in vitro antiproliferativa, atiprotozoárica, anti-herpética e antimicrobiana de 32 extratos orgânicos provenientes de 14 esponjas marinhas e 14 corais coletados no litoral nordestino brasileiro. Os extratos etanólicos das esponjas Amphimedon compressa e Tedania ignis, e o extrato acetônico de Dysidea sp. demonstraram resultados promissores em relação aos efeitos antiproliferativos frente as linhagens celulares A549, HCT-8, PC-3 pelo método da sulforrodamina B, mas sem especificidade. Em relação à atividade antiprotozárica, os extratos etanólico de Amphimedon compressa e acetônico e etanólico de Dysidea sp. apresentaram atividade contra Leishmania amazonensis e Trypanosoma cruzi através do método de expressão de β-galactosidase em células THP-1. Na investigação preliminar de atividade antiviral frente ao vírus Herpes simplex tipo 1 (cepa KOS), os extratos etanólicos das esponjas Amphimedon compressa, Haliclona sp. e Chondrosia collectrix inibiram mais de 50% da replicação viral. O extrato etanólico da esponja Haliclona sp. demonstrou resultados promissores para atividade anti-herpética com altos índices de seletividade para as cepas KOS (IS >50) e 29R (IS>79) frente ao VHS-1 e cepa 333 (IS>108) frente ao VHS-2. O extrato etanólico da esponja Amphimedon compressa exibiu uma pequena atividade contra Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli pelo método de difusão em disco. De acordo com os resultados apresentados, os extratos das esponjas Amphimedon compressa, Tedania ignis e Dysidea sp. serão selecionados para futuros estudos de isolamento e identificação dos compostos bioativos para as atividades antiproliferativa e antiprozoárica. O extrato etanólico de Haliclona sp. será investigado por possuir atividade relevante anti-herpética.

Several species of the genus Passiflora are distributed all over South America, and many of these species are used in popular medicine, mainly as sedatives and tranquilizers. This study analyzes the chemical profile of extracts of four Passiflora species used in folk medicine, focusing on the flavonoids, alkaloids and saponins. We employed simple and fast fingerprint analysis methods by high performance liquid chromatography, ultra performance liquid chromatography and capillary electrophoresis techniques. The analysis led to the detection and identification of C-glycosylflavonoids in all the plant extracts, these being the main constituents in P. tripartita var. mollissima and P. bogotensis. Saponins were observed only in P. alata and P. quadrangularis, while harmane alkaloids were not detected in any of the analyzed extracts in concentrations higher than 0.0187 ppm, the detection limit determined for the UPLC method. Keywords: Passiflora, C-glycosylflavonoids, Alkaloids, HPLC, UPLC, CE

Aristolochia triangularis Cham., is one of the most frequently used medicinal plant in Southern Brazil. Preparations containing the leaves and/or stems are traditionally used as anti-inflammatory, diuretic, as well as antidote against snakebites. This study screened A. triangularis extracts, fractions and isolated compounds for different bioactivities. A weak antiproliferative activity against human lung cancer cell line (A549) was observed only for chloroform fraction obtained from stems (CFstems - CC50: 2.93 µg/mL). Also, a moderate antimicrobial activity against Staphylococcus aureus was detected just for chloroform fraction obtained from leaves (CFleaves -13-16 mm inhibition zone). Additionally, two semi-purified fractions (CFstems-4 and CFleaves-4) selectively inhibited HSV-1 replication (IC50 values of 0.40 and 2.61 µg/mL, respectively), while only CFleaves showed promising results against Leishmania amazonensis. Fractionation of extracts resulted in the isolation of one neolignan (-) cubebin and one lignan (+) galbacin. However, these compounds are not responsible for the in vitro bioactivities herein detected. The presence of aristolochic acid I and aristolochic acid II in the crude ethanol extract of stems (CEEstems) and leaves (CEEleaves) was also investigated. The HPLC analysis of these extracts did not display any peak with retention time or UV spectra comparable to aristolochic acids I and II.

The marine sponge Raspailia bouryesnaultae, collected in South Brazil, was selected for detailed investigation considering the results of a screening that pointed to an in vitro antiproliferative effect against non-small cells of human lung cancer (A549) and anti-herpes activity against Herpes Simplex virus type 1 (KOS and 29R strains) of ethanolic extracts. The fractionation and chemical investigation of the sponge&rsquo, s hexanic fraction led to the isolation and structural elucidation of six clerodane diterpenes. The main component was identified as the already-reported raspailol (1), isolated from a sponge of the same genus collected in New Zealand. The structure of a new diterpene (2) with a rearranged skeleton was established by high-resolution mass spectrometry (HRMS) and 1D and 2D Nuclear magnetic resonance spectroscopy (NMR) experiments, and named here as raspadiene. Furthermore, four diterpenes were elucidated as isomers of clerodane diterpenes previously obtained from plants, namely kerlinic acid (3), kerlinic acid methyl ester (4), annonene (5), and 6-hydroxyannonene (6). They differ in their stereochemistry, since these diterpenes are characterized by a trans ring fusion at the decalin moiety and the relative configuration of the two methyl groups at C-8 and C-9 in a cis relationship (type trans/cis). The Raspailia diterpenes have a cis ring fusion at the decalin moiety, and the two methyl groups at C-8 and C-9 are in a trans relationship (type cis/trans). The isolated compounds were evaluated for their potential antiproliferative effects on human cancer cell line A549, and it was observed that the diterpenes bearing a hydroxyl group at C-6 exhibited moderate cytotoxic activity, with 50% inhibitory concentration (IC50) values lower than 25 &mu, M. The evaluation of the potential anti-herpes activity against Herpes Simplex Virus type 1 (HSV-1, KOS and 29R strains) showed that the more promising results were observed for the new compound 2, since it inhibited HSV-1 (KOS and 29R strains) replication by 83% and 74%, respectively.

Background and purpose Antibiotic resistance is now a worldwide public health problem. A potential alternative source in the search for new antibiotics is the bioactive molecules obtained from marine products, as the halistanol trisulfate, obtained from Petromica citrina, and herein investigated from its antimicrobial and anti-inflammatory properties. Experimental approach The antimicrobial activity of the fractionation products (TSH fraction, halistanol sulfate (HS) and halistanol sulfate C (HS-C)) of the marine sponge Petromica citrina was evaluated against twenty bacteria and two fungi strains by the disk diffusion and microdilution methods. After initial in vitro tests, an in vivo assay was proposed, to evaluate survival and inflammatory parameters in an animal model of peritonitis mediated by MRSA. The animals are treated with TSH fraction (1, 2.5 and 5 mg kg−1) or Vancomycin (30 mg kg−1) twice (6 and 18 h after induction) until organ removal for evaluation of the inflammatory profile, or for 3 days, 12 h each (6 h, 18 h, 30 h, 42 h, 54 h and 66 h after induction) in animals which were followed-up for by five days, for the evaluation of survival. Key results The BF fraction, TSH fraction, HS and HS-Cinhibited, in vitro, the Enterococcus faecalis, Staphylococcus aureus and Candida albicans growth. Moreover, these samples were effective against S. aureus (MSSA), MRSA and Vancomycin-Resistence Enterococcus (VRE). The in vivo results demonstrated that TSH fraction reduced mortality when compared to the saline group. To evaluate the role of inflammation in outcomes of peritonitis, cytokines (IL-1β, IL-6, TNF-α) and MPO activity were measured. In general, anti-inflammatory activity was detected in animals treated with TSH in different doses. Conclusion and implications These data suggest that TSH may be an interesting alternative for the treatment infections by Gram-positive resistant bacteria, due to its antimicrobial profile associated with its anti-inflammatory properties.

In this study we report the synthesis, characterization, biological evaluation, and druglikeness assessment of a series of 20 novel isoxazolyl-sulfonamides, obtained by a four-step synthetic route. The compounds had their activity against Trypanosoma cruzi, Leishmania amazonensis, Herpes Simplex Virus type 1 and cytotoxicity evaluated in phenotypic assays. All compounds have drug-like properties, showed low cytotoxicity and were promising regarding all other biological activities reported herein, especially the inhibitory activity against T. cruzi. The compounds 8 and 16 showed significant potency and selectivity against T. cruzi (GI50 = 14.3 µM, SI > 34.8 and GI50 = 11.6 µM, SI = 29.1, respectively). These values, close to the values of the reference drug benznidazole (GI50 = 10.2 µM), suggest that compounds 8 and 16 represent promising candidates for further pre-clinical development targeting Chagas disease.

Bacterial infection is considered to be one of the most critical health issues of the world. It is essential to overcome this problem by the development of new drugs. Marine organisms as corals, sponges, seaweeds, and other are an incredible source of novel pharmacologically active compounds. Herein, the antimicrobial activity (extract/fractions) of the invasive stony coralTubastraea coccinea was evaluated by the disk diffusion method against 21 microbial strains (ATCC and clinical strains). Micro broth dilution was used to determinate the MIC of the fractions that showed antimicrobial activity by the disk diffusion method. Bioautography assay was also performed. Our results showed that the n-butanol (BF) and aqueous fractions (AF) showed activity against ATCC strains Staphylococcus aureus (MIC 31.25 and 250 μg/mL),Salmonella typhimurium (MIC 125 and 500 μg/mL), Escherichia coli (MIC 62.5 and 500 μg/mL) and Pseudomonas aeruginosa (MIC 62.5 and 500 μg/mL), respectively. Moreover, BF fraction was also effective against the clinical strains S. aureus(MIC 62.5 μg/mL), Klebsiella pneumoniae Carbapenemase—KPC (MIC 125 μg/mL), Methicillin-Resistant Staphylococcus aureus—MRSA (MIC 125 μg/mL) and Vancomycin-Resistant Enterococcus faecalis—VRE (MIC 62.5 μg/mL). The ratio MBC/MIC reinforces the bactericidal profile of BF fraction. The bioautography assay of BF fraction showed the presence of antimicrobial components at Rf0.55.

Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.

Yerba-mate (Ilex paraguariensis St. Hil.) is the most used beverage in Latin America with approximately 426 thousand of tons consumed per year. Considering the broad use of this plant, we aimed to investigate the anxiety-like and stimulant activity of both the hydroethanolic (HE) and aqueous (AE) extracts from leaves of I. paraguariensis. Swiss mice were treated with I. paraguariensis HE or AE chronically or acutely, respectively, followed by evaluation in the elevated plus-maze (EPM; anxiety-like paradigm), open field (OF; locomotor activity) or the step-down avoidance task (memory assessment). Following behavioral protocols the brains were collected for evaluation of acetylcholinesterase (AChE) activity ex vivo. Chronic treatment with HE induced an anxiolytic-like effect and increased motor activity besides augmented AChE activity. Additionally, acute treatment with AE prevented the scopolamine-induced memory deficit in the step-down avoidance task. Overall, our results indicate the importance of the I. paraguariensis-induced CNS effects, since it is a widely used nutraceutical. We have reported anxiolytic, stimulant and neuroprotective effects for this plant species. These effects are potentially modulated by the cholinergic system as well as by caffeine.

In the current study we showed that oral administration of an aqueous extract of Passiflora quadrangularis L., Passifloraceae, pericarp results in a significant prolongation of the sleep duration in mice evaluated in the ethyl ether-induced hypnosis test which indicates sedative effects. Apigenin, the main flavonoid of the extract, induced a similar sedative response when applied alone, at a dose equivalent to that found in the extract, suggesting that apigenin is mediating the sedative effects of P. quadrangularis extract. In addition, the sedative effect of apigenin was blocked by pretreatment with the benzodiazepine antagonist flumazenil (1 mg/kg), suggesting an interaction of apigenin with gamma-aminobutyric acid type A (GABAA) receptors. However, apigenin at concentrations 0.1–50 μM failed to enhance GABA-induced currents through GABAA receptors (α1β2γ2S) expressed in Xenopus oocytes. Nevertheless, based on our results, we suggest that the in vivo sedative effect of the P. quadrangularis extract and its main flavonoid apigenin maybe be due to an enhancement of the GABAergic system. Keywords: Apigenin, Passiflora quadrangularis, Passion flower, Passion fruit, Sedative

Cucurbitacins are natural triterpenoids to which several biological activities are attributed. These molecules can be isolated as free aglycones or as glycosides, despite cucurbitacin glycosides being difficult to be obtained from natural sources. In this work, we report the synthesis of a new 2-β- O -galactoside of dihydrocucurbitacin B and also the synthesis of eight new glycosides containing triazole moiety between the cucurbitane skeleton and the monosaccharidic unit.

The aim of this study was to investigate the sedative activity of the aqueous leaf extract of Passiflora quadrangularis, a species that is widely cultivated and consumed in South America, and to identify its main constituents and elucidate the involvement of the GABAergic pathway in its mechanism of action. The bioguided fractionation of the crude extract showed a positive relationship between the sedative activity of the extract and its flavonoids. The methods employed to identify and isolate its main flavonoids resulted in the identification of vitexin-2''-O-xyloside, vitexin-2''-O-glucoside, orientin-2''-O-xyloside and orientin-2''-O-glucoside. Vitexin-2"-O-xyloside, the major flavonoid of the extract, showed sedative activity after oral administration in mice.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2-amine-cucurbitacin E), which is a semisynthetic derivative of cucurbitacin B, showed potential in vitro synergistic antiproliferative effects combined with paclitaxel (PTX) in A549 cells. In sequence, the purpose of this study was to evaluate the in vivo antitumor efficacy of this combined therapy as well as with these drugs individually, using a human NSCLC xenograft model. Some indicators of sub chronic toxicity that could be affected by treatments were also assessed. The results obtained in vivo with the combined treatment (1 mg/kg + PTX 10 mg/kg) showed the most effective reduction of the relative tumor volume and the highest inhibition of tumor growth and proliferation, when compared with those of the single treatments. Furthermore, scintigraphic images, obtained before and after the treatments, showed that the most effective protocol able to reduce the residual viable tumor mass was the combined treatment. All treatment regimens were well tolerated without significant changes in body weight and no histological and functional damage to liver and kidney tissues. These results corroborate our previous in vitro synergistic effects published. Taken together, these insights are novel and highlight the therapeutic potential of DACE and PTX combination scheme for NSCLC. Fil: Marostica, Lucas Lourenço. Universidade Federal de Santa Catarina; Brasil Fil: de Barros, André Luís Branco. Universidade Federal de Minas Gerais; Brasil Fil: Oliveira, Juliana. Universidade Federal de Minas Gerais; Brasil Fil: Salgado, Breno Souza. Universidade Federal do Espírito Santo; Brasil Fil: Cassali, Geovanni Dantas. Universidade Federal de Minas Gerais; Brasil Fil: Leite, Elaine Amaral. Universidade Federal de Minas Gerais; Brasil Fil: Cardoso, Valbert Nascimento. Universidade Federal de Minas Gerais; Brasil Fil: Lang, Karen Luise. Universidade Federal de Santa Catarina; Brasil Fil: Caro, Miguel Soriano Balparda. Universidade Federal de Santa Catarina; Brasil Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Schenkel, Eloir Paulo. Universidade Federal de Santa Catarina; Brasil Fil: de Oliveira, Mônica Cristina. Universidade Federal de Minas Gerais; Brasil Fil: Simões, Cláudia Maria Oliveira. Universidade Federal de Santa Catarina; Brasil

Five new polyoxygenated marine steroids—punicinols A–E (1–5)—were isolated from the gorgonian Leptogorgia punicea and characterized by spectroscopic methods (IR, MS, 1H, 13C and 2-D NMR). The five compounds induced in vitro cytotoxic effects against lung cancer A549 cells, while punicinols A and B were the most active, with IC50 values of 9.7 μM and 9.6 μM, respectively. The synergistic effects of these compounds with paclitaxel, as well as their effects on cell cycle distribution and their performance in the clonogenic assay, were also evaluated. Both compounds demonstrated significant synergistic effects with paclitaxel. Fil: Moritz, Maria Izabel G.. Universidade Federal de Santa Catarina; Brasil Fil: Marostica, Lucas Lourenço. Universidade Federal de Santa Catarina; Brasil Fil: Bianco, Éverson M.. Universidade Federal de Santa Catarina; Brasil Fil: Rojo de Almeida, Maria Tereza. Universidade Federal de Santa Catarina; Brasil Fil: Carraro, João L.. Universidade Federal do Rio de Janeiro; Brasil Fil: Cabrera, Gabriela Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Palermo, Jorge Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Simoes, Cláudia M. O.. Universidade Federal de Santa Catarina; Brasil Fil: Schenkel, Eloir P.. Universidade Federal de Santa Catarina; Brasil

This review explores the chemical and biological aspects/results reported in the literature of the octocoral species collected at the Brazilian Coast. This article summarizes the biological activities (including pharmacological, antifouling and others related to chemical ecology) for the compounds and/or extracts described elsewhere. Data and references of compounds isolated from species belonging to the same genus, which have not been investigated in Brazil yet, are presented, emphasizing the importance for research in this area. Keywords: Bioactivity, Brazilian Coast, Marine biodiversity, Marine natural products, Octocorallia

The Cecropia genus is widely distributed in Latin America including at least 60 species, and some of them are commonly used in traditional medicine for the treatment of several diseases. We used Cecropia pachystachya Trécul to search for quorum sensing (QS) inhibitors compounds and found that the aqueous extract of C. pachystachya leaves is a promising source of substances with this activity. Using as biosensor Chromobacterium violaceum ATCC 31532 and Escherichia coli pSB403, the compounds chlorogenic acid (2), isoorientin (3), orientin (4), isovitexin (6), vitexin (7), and rutin (9) were identified as QS inhibitors. None of these compounds inhibited the growth of neither the used biosensors nor the microorganisms Staphylococcus aureus ATCC 23591, Escherichia coli ATCC 25922 and Saccharomyces cerevisiae, used here as growth inhibition controls. Along with the rutin, here we presented for the first time the QS-inhibition potential of the C-glycosyl flavonoids. The prospective of this evidence lead to the use of these compounds as antipathogenic drugs or antifoulants.

The leaf extracts of many species of genus Passiflora have been extensively investigated for their biological activities on several rat tissues, but mainly in the central nervous system and liver. They posses anxiolytic-like, sedative effects and antioxidant properties. Evidences suggest a key role of C-glycosylflavonoids in the biological activities of Passiflora extracts. Some species (such as P. manicata) of the genus are still poorly investigated for their chemical and biological activity. In this work, we aim to investigate both antioxidant and antiglycation properties of aqueous extract of P. manicata leaves (PMLE) in vitro and ex vivo models. Crude extract showed the C-glycosylflavonoid isovitexin as the major compound. Isoorientin and vitexin were also identified. In TRAP/TAR assay, PMLE showed a significant antioxidant activity. PMLE at concentrations of 10 and 100 μg mL⁻¹ significantly decreasing LDH leakage in rat liver slices. Antioxidant effect also was observed by decreased in oxidative damage markers in slices hence hydrogen peroxide was added as oxidative stress inductor. PMLE inhibited protein glycation at all concentrations tested. In summary, P. manicata aqueous leaf extract possess protective properties against reactive oxygen species and also protein glycation, and could be considered a new source of natural antioxidants.

Several Passiflora species have been used widely as a folk medicine due to their sedative and anxiolytic activities. In Brazil, a number of native plants of the genus Passiflora exist, but only Passiflora edulis f. flavicarpa (PE) and Passiflora alata (PA) are of commercial value. Thus, the aim of the present study was to investigate the sedative effects of aqueous extracts obtained from the pericarp as well as from the leaves of PE and PA in mice using radiotelemetry. Aqueous extracts from PE and PA were tested for effects on locomotion over 180 min in 300 mg/kg, 600 mg/kg and 1200 mg/kg, in male C57BL/6J mice after oral administration. For validation of the telemetry system, caffeine (negative control) and midazolam (positive control) were used. All tested extracts decreased locomotor activity in a dose-dependent manner in comparison to the control group. The two lower concentrations of each extract showed the highest decrease in locomotion after 24 min, while 1200 mg/kg had a significant sedative effect already after 18 min. Interestingly, aqueous extracts of PA were more active in comparison to aqueous extracts of PE and the pericarp extracts of both plants showed more pronounced effects on locomotor activity if compared to leaf extracts. In conclusion, the present study represents an innovative, objective approach to measure sedative effects of plant extracts with minimized handling-related stress and remote data collection.

Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cuc1) isolated from Wilbrandia ebracteata on human non-small-cell lung cancer (A549). In order to achieve this aim, the cell proliferation was measured by MTT assay and actin cytoskeleton was stained by rhodamine-phalloidin, whereas, the cell cycle distribution and apoptosis induction were quantified using flow cytometry. The signal transduction profiling of Cuc1 treated cells, as well as the levels of apoptotic proteins were analyzed by Western blotting. Cuc1 significantly inhibited cell growth showing IC50 values of 13.5±1.8 and 3.8±0.4 μM for 48 and 72 h of treatment, respectively. Additionally, Cuc1 arrested cell cycle at G2/M phase, disrupted the actin dynamics and induced apoptosis since the amount of apoptotic cells increased from 5.18±0.585% in the untreated cells to 73.82±0.545% in the treated cells. Detailed analysis on the mechanism of action revealed that Cuc1 inhibited the phosphorylation of Protein Kinase B (PKB/AKT) and Signal Transducer and Activator of Transcription (STAT3) signaling pathways, down-regulating the expression of Bcl-2 and consequently inducing cytochrome c release from the mitochondria to the cytosol. These results suggest that the Cuc1 could be a potential candidate for cancer chemotherapy agent. Fil: Silva, I. T.. Universidade Federal de Santa Catarina; Brasil Fil: Teixeira, Marina R.. Universidade Federal de Santa Catarina; Brasil Fil: Lang, Karen L.. Universidade Federal de Santa Catarina; Brasil Fil: Guimarães, Tatiana da R.. Universidade Federal de Santa Catarina; Brasil Fil: Dudek, Sabine E.. University of Münster; Alemania Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Ludwig, Stephan. University of Münster; Alemania Fil: Caro, Miguel S. B.. Universidade Federal de Santa Catarina; Brasil Fil: Schenkel, Eloir P.. Universidade Federal de Santa Catarina; Brasil Fil: Simoes, Cláudia M. O.. Universidade Federal de Santa Catarina; Brasil

Cucurbitacins are secondary metabolites that mediate insect plant interactions not only as allomones against generalists but also as kairomones for specialist herbivores. This study was undertaken to identify the potential of cucurbitacin derivatives as insect antifeedant agents. The antifeedant capacity against a Cucurbitaceae specialist [Epilachna paenulata (Coleoptera: Coccinellidae)] and a polyphagous insect [Pseudaletia adultera (Lepidoptera: Noctuidae)] was evaluated in preference tests in which the insects were given a choice between food plants either treated with the cucurbitacin derivatives or treated with the solvent. The activity was found not to be related to the basic cucurbitacin skeleton, as only 15 of the 28 tested cucurbitacin derivatives were active. Only one of the tested compounds was phagostimulant to the specialist insect (the hemissuccinate of 16-oxo-dihydrocucurbitacin B derivative), while all other active derivatives were deterrent against one of the insects (13 compounds) or both of them (3 compounds). Changes in ring A of the cucurbitacins, as well as in the side chain, modified the activity. As a general trend, when chemical modifications of the basic structure produced a change in activity, the response was opposite in both insects used as biodetectors, indicating that a selective variation in the activity may be achieved by chemical modifications of the cucurbitacin skeleton. Fil: Lang, Karen L.. Universidade Federal de Santa Catarina; Brasil Fil: Deagosto, Emilio. Universidad de la República; Uruguay Fil: Zimmermann, Lara Almida. Universidade Federal de Santa Catarina; Brasil Fil: Machado, Vanessa Rocha. Universidade Federal de Santa Catarina; Brasil Fil: Bernardes, Lílian Sibelle Campos. Universidade Federal de Santa Catarina; Brasil Fil: Schenkel, Eloir P.. Universidade Federal de Santa Catarina; Brasil Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Palermo, Jorge Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Rossini, Carmen. Universidad de la República; Uruguay

The species of Passiflora are widely used in folk medicine as mild sedatives and tranquilizers. P. alata and P. quadrangularis are distributed throughout South America, with widespread occurrence in Brazil and Colombia. Due to the difficulty in making a botanical distinction between these species, especially in the absence of flowers and fruits, the use of chemical markers for these plants offer an alternative method of identification. This work describes the isolation and identification of the major flavonoids and saponins from the leaves of P. alata and P. quadrangularis, as well as rapid and efficient HPLC-DAD methods for comparison of these compounds in both species. Vitexin derivatives are proposed as chemical markers in the identification of P. alata and P. quadrangularis and the detection of adulterations in raw material.

Investigation of the crude ethanolic extract obtained from the aerial parts of Dodonaea viscosa led to the isolation of three new ent-labdane diterpenes (1–3). The structures were established on the basis of their ESI–MS, UV, IR and NMR spectral data. The crude extract, fractions and compounds were evaluated for in vitro antiviral activity against Herpes Simplex Virus type 1 (HSV-1). The crude extract showed promising antiherpes activity expressed by a selectivity index of 6.2.

Climate change can be associated with variations in the frequency and intensity of extreme temperatures and precipitation events on the local and regional scales. Along coastal areas, flooding associated with increased occupation has seriously impacted products and services generated by marine life, in particular the biotechnological potential that macroalgae hold. Therefore, this paper analyzes the available information on the taxonomy, ecology and physiology of macroalgae and discusses the impacts of climate change and local stress on the biotechnological potential of Brazilian macroalgae. Based on data compiled from a series of floristic and ecological works, we note the disappearance in some Brazilian regions of major groups of biotechnological interest. In some cases, the introduction of exotic species has been documented, as well as expansion of the distribution range of economically important species. We also verify an increase in the similarities between the Brazilian phycogeographic provinces, although they still remain different. It is possible that these changes have resulted from the warming of South Atlantic water, as observed for its surface in southeastern Brazilian, mainly during the winter. However, unplanned urbanization of coastal areas can also produce similar biodiversity losses, which requires efforts to generate long-term temporal data on the composition, community structure and physiology of macroalgae.

Two cucurbitacins, dihydrocucurbitacin B (1) and cucurbitacin B (2), which can be obtained in large amounts from the roots of Wilbrandia ebracteata and from the fruits of Luffa operculata, respectively, were used as starting materials for the preparation of a library of 29 semi-synthetic derivatives. The structural changes that were performed include the removal, modification or permutation of functional groups in rings A and B as well as in the side chain. All new semisynthetic compounds, as well as 1 and 2, were tested in vitro for their cytotoxic effects on non-small-cell lung cancer cells (A549 cells). Some of these compound displayed potent to moderate activity against A549 tumor cells, especially those cucurbitacin B derivatives which were modified at ring A.

The antiherpes effects of the crude extract obtained from Ilex paraguariensis leaves (yerba mate) and their purified fractions were investigated. The most active fraction was selected and assayed to determine the viral multiplication steps upon which it acted. In order to detect the major components of this fraction, thin layer chromatography (TLC) analysis was performed. The antiviral activity was evaluated against HSV-1 and HSV-2 by a viral plaque number reduction assay (IC(50) ) and the cytotoxicity by a MTT assay (CC(50) ). According to the obtained results, all tested samples showed antiherpes activity at noncytotoxic concentrations, and the ethyl acetate fraction was the most active (SI = CC(50) /IC(50) = 188.7 and 264.7 for HSV-1 and HSV-2, respectively). The results also demonstrated that this fraction exerts antiviral activity by the reduction of viral infectivity, the inhibition of virus entry into cells and cell-to-cell virus spread, as well as by the impaired levels of ICP27, ICP4, gD and gE proteins of HSV-1. The TLC analysis showed that this fraction contains monodesmosidic triterpenoid saponins, matesaponin-1 (a bidesmosidic one), caffeic and chlorogenic acids and rutin, which suggests that they could act synergistically and be responsible for the detected antiherpes activity.

Introduction Leaves and fruits of Passiflora species are widely used around the world in popular medicine, mainly as sedatives and tranquilisers. C-glycosyl flavonoids are the main components of these species. Objective To investigate the constituent patterns and to develop a chromatographic method for the characterisation of the C-glycosyl flavonoids profile of the extracts of the leaves and the pericarp of South American Passiflora species. Methodology The chemical composition of extracts from the leaves and the fruits' pericarp of Passiflora edulis var. flavicarpa, P. edulis var. edulis, Passiflora alata, Passiflora tripartita var. mollissima, Passiflora quadrangularis, Passiflora manicata and Passiflora ligularis was evaluated for the presence of C-glycosyl flavonoids. Two separate HPLC methods were developed suitable for a diode array detector (DAD) and a MS detector. Separation by HPLC-DAD was achieved on a Luna C-18 column, using solvent A (tetrahydrofuran–isopropanol–acetonitrile) and solvent B (H3PO4 0.5%) in an isocratic elution mode. In the HPLC-MS, the components were separated on a Luna RP-18A column by a gradient elution (water–acetonitrile–formic acid). Results The presence of C-glycosyl flavonoids was identified in leaves and pericarp of P. edulis var. flavicarpa, P. alata, P. edulis var. edulis and P. tripartita var. molissima, but only in leaf extracts of P. quadrangularis and P. manicata and not at all in P. ligularis. The different species and varieties showed different major constituents. The C-glycosyl flavonoids identified more frequently were orientin, isoorientin, vitexin and isovitexin. Conclusion The methods established are simple and can be used as a tool for the characterisation and quality control of pharmaceutical preparations containing these Passiflora extracts. Copyright © 2011 John Wiley & Sons, Ltd.

An efficient and reproducible HPLC-DAD method was developed and validated for the simultaneous quantification of major compounds (chlorogenic acid, isoorientin, orientin and isovitexin) present in the leaves of two Cecropia species, C. glaziovii and C. pachystachya. From the leaves of C. glaziovii and C. pachystachya were isolated the C-glycosylflavones isoorientin and isovitexin and identified on both species chlorogenic acid (3-O-caffeoylquinic acid) and the O-glycosylflavonol isoquercitrin. The C-glycosylflavone orientin was isolated only from C. pachystachya. Chlorogenic acid was the major compound in both species (11.1 mg g-1 of extract of C. glaziovii and 27.2 mg g-1 of extract of C. pachystachya) and for the flavonoids quantified, isovitexin was the main C-glycosylflavonoid for C. glaziovii (4.6 mg g-1 of extract) and isoorientin the main one for C. pachystachya (17.3 mg g-1 of extract). Um método eficiente e reprodutível por CLAE-DAD foi desenvolvido e validado para quantificação simultânea dos compostos fenólicos majoritários (ácido clorogênico, isoorientina, orientina e isovitexina) presentes nas folhas de duas espécies de Cecropia, C. glaziovii e C. pachystachya. Das folhas de C. glaziovii e C. pachystachya foram isolados os flavonoides C- glicosídeos isoorientina e isovitexina e identificados em ambas as espécies o ácido clorogênico (ácido 3-O-cafeoilquínico) e o flavonoide O-glicosídeo isoquercitrina. O flavonoide C-glicosídeo orientina foi isolado apenas da espécie C. pachystachya. O ácido clorogênico mostrou-se como composto majoritário em ambas as espécies analisadas (11,1 mg g-1 de extrato de C. glaziovii e 27,2 mg g-1 de extrato de C. pachystachya), e em relação aos flavonoides quantificados, isovitexina se apresentou como o flavonoide C-glicosídeo majoritário para C. glaziovii (4,6 mg g-1 extrato) e isoorientina majoritário para C. pachystachya (17,3 mg g-1 de extrato)

Five saponins purified from the leaves of three Ilex species (saponins 1 and 2 from I. dumosa; saponin 3 from I. argentina; saponin 4 from I. paraguariensis) and from Passiflora alata (saponin 5) were evaluated for their in vitro haemolytic activity and in vivo immunostimulatory ability in a mouse model using tetanus toxoid (TT) as a model antigen. The assayed saponins showed very weak or no haemolytic activity over the tested concentration range. Mice were immunized twice with TT formulated with pure saponins 1-5, or with a mixture of saponins from Quillaja saponaria, aluminum hydroxide gel or saline, which were used as controls. The elicited humoral response was evaluated by means of the time course of specific serum antibody levels up to day 131 post-priming (total IgG and isotypes); the cellular response was tested through a delayed-type hypersensitivity (DTH) assay. The assayed saponins, in particular saponins 3 and 5, showed an adjuvant effect similar to that of alum for all tested parameters. The immunostimulating potential of these compounds deserves further investigation, especially taking into account that some Ilex spp. and Passiflora alata are native crops of widespread use and economical importance in Latin America.

Neste trabalho, é analisada a situação dos processos judiciais contra a Secretaria de Estado de Saúde de Santa Catarina determinando fornecimento de medicamentos em 2003 e 2004. As variáveis consideradas foram: patologia declarada, medicamento solicitado, origem da prescrição, possíveis alternativas terapêuticas na Relação Estadual de Medicamentos (Resme), registro dos medicamentos na Agência Nacional de Vigilância Sanitária (Anvisa) e custos totais. Foram analisados 622 processos, com gasto de R$ 11.333.750,00. Os serviços privados de saúde originaram 56% das prescrições. Hepatite C e artrite reumatoide foram as doenças mais referidas. Em 40% dos casos, os produtos faziam parte da Resme. Dos produtos solicitados, 6,2% tiveram a sua comercialização iniciada no Brasil a partir do ano 2000, destacando-se Interferon Pequilado e Infliximabe, responsáveis por 46% do total dos gastos. Alguns processos envolviam medicamentos que não possuíam registro na Anvisa, e houve casos em que a indicação de uso do medicamento não estava aprovada no país. Os resultados indicam que a reavaliação dos elencos de medicamentos padronizados e a melhoria no acesso aos tratamentos, aliadas à melhor divulgação dos programas de distribuição de medicamentos, são medidas que potencialmente poderão reduzir o número de processos judiciais.This study describes the situation of lawsuits concerning the access to medical products by the Health Department of Santa Catarina State (SES/SC), Brazil, during the years of 2003 and 2004. The variables considered were: declared illnesses, medicines demanded, prescription origin, possible alternatives therapeutics in the Santa Catarina State Register of Essential Medicines (Resme), the medicines registration at the National Health Surveillance Agency (Anvisa) and total expenditure. 622 lawsuits were filed. Total expenditure was R$ 11,333,750,00 (Brazilian Reais). Private health care was the source of 56% of the prescriptions. Hepatitis C and rheumatoid arthritis were the most commonly diseases involved. About 40% of requested drugs were on the Resme. 6.2% of required drugs were approved in Brazil after 2000. PEG-Interferon and Infliximab were responsible for 46% of total expenditure. There were still some cases of drugs or indications not registered at Anvisa. These results indicate the need to reassess the list of medicines regularly provided by the SES/SC, and also to improve accessibility to (and information concerning) Programs of medicines distribution. These measures may potentially reduce the number of lawsuits filed against the State.

Neste trabalho, é analisada a situação dos processos judiciais contra a Secretaria de Estado de Saúde de Santa Catarina determinando fornecimento de medicamentos em 2003 e 2004. As variáveis consideradas foram: patologia declarada, medicamento solicitado, origem da prescrição, possíveis alternativas terapêuticas na Relação Estadual de Medicamentos (Resme), registro dos medicamentos na Agência Nacional de Vigilância Sanitária (Anvisa) e custos totais. Foram analisados 622 processos, com gasto de R$ 11.333.750,00. Os serviços privados de saúde originaram 56% das prescrições. Hepatite C e artrite reumatoide foram as doenças mais referidas. Em 40% dos casos, os produtos faziam parte da Resme. Dos produtos solicitados, 6,2% tiveram a sua comercialização iniciada no Brasil a partir do ano 2000, destacando-se Interferon Pequilado e Infliximabe, responsáveis por 46% do total dos gastos. Alguns processos envolviam medicamentos que não possuíam registro na Anvisa, e houve casos em que a indicação de uso do medicamento não estava aprovada no país. Os resultados indicam que a reavaliação dos elencos de medicamentos padronizados e a melhoria no acesso aos tratamentos, aliadas à melhor divulgação dos programas de distribuição de medicamentos, são medidas que potencialmente poderão reduzir o número de processos judiciais.

Seven new (1-7) and seven previously reported (8-14) halogenated metabolites were isolated from the organic extract of the Brazilian red alga Laurencia catarinensis. The structure elucidation and the assignment of the relative configurations of the new natural products were based on detailed NMR and MS spectroscopic analyses, whereas the structure of metabolite 6 was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of metabolite 1 was determined using the modified Mosher's method. The in vitro cytotoxicity of compounds 1-14 was evaluated against HT29, MCF7, and A431 cell lines.

The alga Acanthophora spicifera (Vahl) Borgesen (Ceramiales: Rhodophyta) is a rhodophycean alga with wide distribution throughout the tropics and subtropics (Kilar and McLachlan, 1986) and one of the most abundant red algal species found on reef flats (Joikel and Morrissey, 1986). Investigation with this species is rather scarce (Aihara and Yamamoto, 1968; Wahidulla et al., 1986, 1991, 1998; Wahidulla and Kamat, 1991; Prakash et al., 1989; Wang et al., 1998, 2003). Therefore, as a part of the systematic chemical research with rhodophycean algae, we report here the results concerning the main sterols isolated from A. spicifera, an abundant alga in Southern Brazil. Fil: Lang, Karen L.. Universidade Federal de Santa Catarina; Brasil Fil: Palermo, Jorge Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Falkenberg, Miriam. Universidade Federal de Santa Catarina; Brasil Fil: Schenkel, Eloir P.. Universidade Federal de Santa Catarina; Brasil

Mate (Ilex paraguariensis A. St. Hil.) is a shade-tolerant species, frequently cultivated on agroforestry systems or even in monoculture. Secondary metabolism of mate includes the methylxanthines, caffeine and theobromine. Shading could alter the quantitative profile of these compounds in the plant, and since the secondary chemistry of mate is decisive to determine the quality of raw material, the caffeine and theobromine content under different light intensities were investigated. Artificial shading obtained by a nylon screen and natural shading produced by other trees were tested. Methylxanthines content was increased with the reduction of light, but only in the low light intensity treatment. A negative correlation was found between biomass accumulation and methylxanthines content. But the total methylxanthines yield per plant was not altered.

The aqueous leaves extracts of Passiflora alata (100-300 mg/kg, i.p.) and Passiflora edulis (100-1000 mg/kg, i.p.) possess a significant antiinflammatory activity on carrageenan-induced pleurisy in mice. Treatment with the extracts inhibited leukocyte migration and reduced the formation of exudate. Moreover, a significant inhibition of myeloperoxidase and adenosine-deaminase activities was observed at the doses tested (100 or 250 mg/kg, i.p.). At the same doses, a significant decrease of serum C-reactive protein was observed.

The popular medicine Passiflora edulis has been used as a sedative, tranquilizer, against cutaneous inflammatory diseases and intermittent fever. Most of the pharmacological investigations of Passiflora edulis have been addressed to its Central Nervous System activities, such as anxiolytic, anticonvulsant and sedative actions. Otherwise, there are few reports about the anti-inflammatory activity of the Passiflora species. The aim of this study was to investigate the mechanism of the anti-inflammatory effect of aqueous lyophilized extract obtained from leaves of Passiflora edulis var. flavicarpa Degener (Passifloraceae) in the mouse model of pleurisy induced by carrageenan (Cg), bradykinin, histamine or substance P, observing the effects upon leucocytes migration, myeloperoxidase (MPO), nitric oxide (NO) concentrations and tumor necrosis factor-alpha (TNFα) and interleukin-1 beta (IL-1β) levels. Results: Passiflora edulis (250 mg/kg) administered by intraperitoneal route (i.p.) inhibited the leukocyte, neutrophils, myeloperoxidase, nitric oxide, TNFα and IL-1β levels (P < 0.01) in the pleurisy induced by carrageenan. Passiflora edulis (250-500 mg/kg, i.p.) also inhibited total and differential leukocytes in the pleurisy induced by bradykinin, histamine or substance P (P < 0.05). Conclusion: Several mechanisms, including the inhibition of pro-inflammatory cytokines (TNFα, IL-1β), enzyme (myeloperoxidase) and mediators (bradykinin, histamine, substance P, nitric oxide) release and/or action, appear to account for Passiflora edulis's actions.