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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.

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.

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.

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.

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 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.

The aim of this study was to investigate the anti-inflammatory effect of the aqueous extract of Passiflora edulis forma flavicarpa Degenerer leaves in the air pouch inflammation model induced by carrageenan, histamine or substance P, in mice. An aqueous extract was prepared by infusion and lyophilized. Part of the extract was fractionated with n-butanol, resulting in the butanolic and aqueous residual fractions. The anti-inflammatory activities of the lyophilized extract and these two derived fractions were evaluated. In the inflammation induced by carrageenan, aqueous extract (100 mg/kg, i.p.), butanolic fraction (50 mg/kg, i.p.), aqueous residual fraction (100 mg/kg, i.p.) and dexamethasone (0.5 mg/kg, i.p.) inhibited the leukocyte, neutrophil, myeloperoxidase, nitric oxide, and interleukin-1 beta (IL-1β) levels (p < 0.05). The aqueous extract and butanolic and aqueous residual fractions, but not dexamethasone, decreased macrophage inflammatory protein-2 (MIP-2) levels (p < 0.05). Only dexamethasone inhibited mononuclear cells (p < 0.01). In the inflammation induced by histamine, the aqueous extract, butanolic and aqueous residual fractions, and dexamethasone inhibited total and differential leukocytes (p < 0.01). In the inflammation induced by substance P, the aqueous extract, butanolic and aqueous residual fractions, and dexamethasone also inhibited total leukocytes and mononuclears (p < 0.01). Neutrophils were only inhibited by aqueous extract, butanolic fraction, and dexamethasone (p < 0.05). In conclusion, the active principle(s) present in the P. edulis aqueous extract and its two fractions showed pronounced anti-inflammatory properties, inhibiting cell migration, proinflammatory cytokines, enzymes and mediators.

From the fresh aerial parts of Senecio selloi (Asteraceae), two diastereomeric triterpenes with a hitherto unknown skeleton have been isolated. The structure has been elucidated mainly by advanced NMR experiments, including inverse techniques, HMQC, HMBC, ROESY.

Brazilian plants are potential sources of useful edible and medicinal plants. Hydromethanolic extracts prepared from 54 medicinal plants used in folk medicine to treat infections were screened for antiviral properties against five different viruses (HSV-1, HSV-2, poliovirus type 2, adenovirus type 2 and VSV). Fifty-two percent of the plant extracts exhibited antiviral against one or more tested viruses. More specifically, 42.6% showed activity against HSV-1 (herpes simplex virus type 1), 42.6% against HSV-2 (herpes simplex virus type 2), 26% against poliovirus and 24% against VSV (vesicular stomatitis virus). None of the extracts was active against adenovirus. Trixis praestans (Vell.) Cabr. and Cunila spicata Benth. extracts were further characterized for antiviral activity.

The essential oils of cultivated and wild-growing Cunila microcephala and C. fasciculata from southern Brazil were analysed by GC, GC-mass spectrometry and 13 C NMR spectroscopy. The main constituent in both species was found to be menthofuran (82.3–85.1% in C. microcephala and 71.6–76.4% in C. fasciculata ). Other compounds in significant amounts were limonene (2.1–3.8% in C. microcephala and 8.6–11.2% in C. fasciculata ) and β-caryophyllene (3.3–3.9% in C. microcephala and 3.5–4.2% in C. fasciculata ). The chemotaxonomic and toxicologic aspects of menthofuran accumulation are discussed.

Three new compounds, docosanoic cinnamate, 7-hydroperoxy-5,6-E-dehydro-6,7-dihydronerol and 2-(3-methylbut-3-enyl)-3-methyl-2,5-dihydrofuran were isolated from the leaves of Heterothalamus alienus and their structures determined by spectroscopical methods.

Three new cucurbitacins were isolated from the roots of Wilbrandia ebracteata and their structures established as 16α, 23α-epoxy-2β,3β,20β-trihydroxy-10α,23β-cucurbit-5,24-dien-11-one, 16α,23α-epoxy-2β,3β,20β-trihydroxy- 10α,23α-cucurbit-5,24-dien-11-one and 2β,3β,16α,20,25-pentahydroxy-10α-cucurbit-5,23-dien-11-one, mainly by spectroscopy.

Baccharis ochracea contains a new diterpene in addition to the known compounds chlorogenic acid, isochlorogenic acid, α-spinasterol and isoquercitrin. The diterpene is a geranylgeraniol derivative with a butenolide ring.

Ethanolic extracts from leaves and roots of Ateleia glazioviana (Leguminosae-Papilionoideae) and the saponin containing fraction from Thinouia coriacea (Sapindaceae) have been studied for ichthyotoxic activity on Phallocerus caudimaculatus and Geophagus brasiliensis. The ethanolic extracts were used in doses ranging from 50 to 100 ppm, based on the dry residue. The saponin fraction was used at doses of 1-10 ppm. The two plant extracts and saponin fractions were found to be ichthyotoxic, justifying their traditional role as an aid in fishing.