Maytenus ilicifolia (Celastraceae) is a medicinal plant that is native to southern Brazil and is popularly known as “espinheira-santa”. From a biosynthesis perspective, this species accumulates quinonemethide triterpenes and sesquiterpene pyridine alkaloids as major secondary metabolites that exhibit interesting biological properties, with antitumoral and antiprotozoal activities, respectively, being the most frequently reported. Additionally, the restricted accumulation of such compounds in the roots raises questions about the expression of proteins involved in such compartmentalization and their possible biological and/or ecological role in M. ilicifolia. Thus, this article describes the use of shotgun proteomics and histochemical studies for the characterization of the main biosynthetic pathways involved in the regulation of the metabolism in M. ilicifolia roots. This combined approaches also resulted in the identification of a series of proteins involved in the quinonemethide triterpenes and sesquiterpene pyridine alkaloids, providing evidences of their differential compartmentalization.

The known kavalactones (E)-4-methoxy-6-styryl-2H-pyran-2-one, 4-methoxy-6-(3-phenyloxiran-2-yl)-2H-pyran-2-one, 6-(1,2-dihydroxy-2-phenylethyl)-4-methoxy-2H-pyran-2-one, the three benzoic acid derivatives methyl-4-methoxy-3-(3'-methyl-2'-butenyl)benzoate and methyl 2,2-dimethyl-4-oxochroman-6-carboxylate, and a new methyl 4-methoxy-3-(3-methylbut-2-enoyl)benzoate were isolated from the ethanolic extract of Piper fuligineum. The structures of these compounds were determined by using a combination of spectroscopic methods, including 1D- and 2D-nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. This is the first report of the chemical study of P. fuligineum, and the methyl 4-methoxy-3-(3-methylbut-2-enoyl)benzoate is described as a new natural product.

ABSTRACT The hemoflagellate protozoan, Trypanosoma cruzi, mainly transmitted by triatomine insects through blood transfusion or from mother-to-child, causes Chagas' disease. This is a serious parasitic disease that occurs in Latin America, with considerable social and economic impact. Nifurtimox and benznidazole, drugs indicated for treating infected persons, are effective in the acute phase, but poorly effective during the chronic phase. Therefore, it is extremely urgent to find innovative chemotherapeutic agents and/or effective vaccines. Since piplartine has several biological activities, including trypanocidal activity, the present study aimed to evaluate it on two T. cruzi strains proteome. Considerable changes in the expression of some important enzymes involved in parasite protection against oxidative stress, such as tryparedoxin peroxidase (TXNPx) and methionine sulfoxide reductase (MSR) was observed in both strains. These findings suggest that blocking the expression of the two enzymes could be potential targets for therapeutic studies.

Piper gaudichaudianum Kunth (Piperaceae) accumulates gaudichaudianic acid, a prenylated benzopyran, as its major component. Interestingly, this trypanocidal compound occurs as a racemic mixture. Herein, transcriptomic investigations of Piper gaudichaudianum using the RNA-seq approach are reported, and from the analysis of the transcripts expressed it was possible to propose a complete biosynthetic pathway for the production of gaudichaudianic acid, including the steps that originate its precursor, p-hydroxybenzoic acid. Peperomia obtusifolia (L.) A. Dietr. (Piperaceae) also accumulates racemic benzopyrans, however, its chromanes originate from the polyketide pathway, while the chromenes from Piper derives from the shikimate pathway. Recent transcriptomic and proteomic studies of the former species did not identify polyketide synthases involved in the production of the benzopyran moiety, but revealed the expression of tocopherol cyclase, which may be responsible for the cyclization of the 3,4-dihydro-2H-pyran ring. The analysis of the enzymes involved in the secondary metabolism of Piper gaudichaudianum and the comparison with the data previously obtained from Peperomia obtusifolia can provide valuable information on how these compounds are biosynthesized.

The Coordination for the Improvement of High Education Personnel (CAPES), the Brazilian federal agency for graduate programs, plays a fundamental role for the expansion and consolidation of the National Postgraduate System (SNPG) and the execution of the National Graduate Plan (PNPG) 2011-2020. In this paper, we discuss the evolution of the Brazilian graduate program in chemistry and its role in the formation of highly qualified professionals in chemistry (academic master’s degree, professional master’s degree and doctoral degree) for the academy, teachers and lecturers for all levels of the education system, as well for the non-academic market.

Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for discovering antimetastatic agents because this process is fundamental to metastasis. Piperlongumine, selected from cell-based assay screening of NuBBE Database, inhibited the migration of MDA-MB-231 breast cancer cells with an EC50 of 3.0 ± 1.0 µM by the Boyden chamber assay. A series of five analogous compounds based on the structure of piperlongumine were designed, synthesized and evaluated in cell migration and cytotoxicity assays. The analogue designed by molecular simplification ((E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide) was the most active of the series, with an EC50 of 1.5 ± 1 µM. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4.

The use of natural products has definitely been the most successful strategy in the discovery of novel medicines. Secondary metabolites from terrestrial and marine organisms have found considerable use in the treatment of numerous diseases and have been considered lead molecules both in their natural form and as templates for medicinal chemistry. This paper seeks to show the great value of secondary metabolites and emphasize the rich chemical diversity of Brazilian biodiversity. This natural chemical library remains understudied, but can be a useful source of new secondary metabolites with potential application as templates for drug discovery.

Phytochemical investigations on three Brazilian Lauraceae species from the Cerrado region of São Paulo State, Ocotea corymbosa (Meins) Mez., O. elegans Mez. and Persea pyrifolia Nees & Mart. ex Nees resulted in the isolation of flavonoids, an ester of the 4-O-E-caffeoylquinic acid, an aromatic sesquiterpene besides furofuran lignans. This is the first chemical study on the leaves of Ocotea elegans and O. corymbosa as well as the first report of non-volatile compounds from Persea pyrifolia.

Espécies reativas do oxigênio (ERO) e radicais livres estão relacionados ao início ou à exacerbação de muitas doenças em organismos vivos; existindo portanto uma necessidade contínua por moléculas antioxidantes que inativem as ERO e radicais livres. Muitos estudos com extratos brutos de plantas têm demonstrado propriedades antioxidantes e seqüestradoras de radicais livres. Espécies de Salacia são utilizadas, em muitos países, como remédio tradicional contra certas doenças e por suas propriedades antiinflamatórias. Neste estudo, o extrato bruto etanólico da casca da raiz da Salacia campestris Walp (Hippocrateaceae) foi avaliado quanto à sua habilidade em seqüestrar radicais livres e espécies reativas do oxigênio; os resultados são expressos como porcentagem de inibição das espécies ativas. ScEtOH mostrou-se eficiente frente as espécies estudadas: radical DPPH (inibição obtida = 30%), ABTS•+ (IC50 = 1,8±0,8 μg/mL), HOCl (IC50 = 1,7 ± 0,1 μg/mL), O2•- (inibição obtida = 32%), and NO• (inibição obtida = 18%). A inibição da atividade peroxidásica foi avaliada através da oxidação do guaiacol catalisada pela hemina, HRP e mieloperoxidase (MPO); os dados mostram que 10 μg/mL de ScEtOH promovem 54 e 51% de inibição, respectivamente para os sistemas da hemina e da HRP. No sistema da MPO, ScEtOH promoveu 50% de inibição na dose de 8,9 μg/mL, enquanto a quercetina, um potente inibidor da MPO promoveu tal inibição com 1,35 μg/mL.

Reactive oxygen species (ROS) and free radical species have been implicated in initiating or accompanying many diseases in living organisms; there is thus, a continual need for antioxidants molecules to inactivate ROS/free radicals. Many studies of plants crude extracts have demonstrated free-radical scavenging and antioxidant action. Salacia species have long been used, in several countries, as traditional medicines against certain diseases and for their anti-inflammatory properties. In this study, Salacia campestris Walp (Hippocrateaceae) root bark ethanol extract (ScEtOH) was assessed for its ability to scavenge free radicals and reactive oxygen species; the results were expressed as percentage inhibition of the active species. ScEtOH was efficient against studied species: DPPH radical (obtained inhibition = 30%), ABTS•+ (IC50 = 1.8±0.8 μg/mL), HOCl (IC50 = 1.7 ± 0.1 μg/mL), O2•- (obtained inhibition = 32%), and NO• (obtained inhibition = 18 %). Peroxidase activity inhibition was evaluated through the guaiacol oxidation reaction catalyzed by hemin, HRP and myeloperoxidase (MPO); data showed that ScEtOH at 10 μg/mL led to 54 and 51% of inhibition, respectively, for the hemin and HRP systems. In the MPO system, ScEtOH promoted a 50% inhibition at 8.9 μg/mL, whereas quercetin, a powerful MPO inhibitor, inhibited this system at 1.35 μg/mL.

No escopo de nossas pesquisas sobre agentes bioativos da flora brasileira, vinte e quatro extratos e frações de Piper arboreum Aub. e Piper tuberculatum Jacq. (Piperaceae) tiveram sua atividade tripanocida avaliada através do ensaio colorimétrico com MTT. As atividades mais potentes foram manifestadas pelas frações hexânicas das folhas de P. arboreum (CI50 = 13,3 µg/mL) e P. tuberculatum (CI50 = 17,2 µg/mL). As frações hexânicas dos frutos de P. tuberculatum e P. arboreum também apresentaram efeito tóxico potente contra as formas epimastigotas de Trypanosoma cruzi, com valores de CI50 (µg/mL) de 32,2 e 31,3, respectivamente. Adicionalmente, o estudo fitoquímico da fração hexânica das folhas de P. arboreum forneceu duas amidas pirrolidínicas, piperilina (1) e 4,5-diidropiperilina (2), que podem ser responsáveis pela atividade antiprotozoária desta fração.

In the scope of our ongoing research on bioactive agents from Brazilian flora, twenty-four extracts and fractions obtained from Piper arboreum Aub. and Piper tuberculatum Jacq. (Piperaceae) were screened for trypanocidal activity by using MTT colorimetric assay. The strongest activity was found in hexane fractions from the leaves of P. arboreum (IC50= 13.3 µg/ mL) and P. tuberculatum (IC50 = 17.2 µg/mL). Hexane fractions of the fruits of P. tuberculatum and P. arboreum showed potent toxic effects on epimastigote forms of Trypanosoma cruzi, with values of IC50 (µg/mL) of 32.2 and 31.3, respectively. Additionally, the phytochemical study of the hexane fraction of P. arboreum leaves furnished two pyrrolidine amides, piperyline (1) and 4,5-dihydropiperyline (2), which could be responsible, at least in part for the observed antiprotozoal activity.

The phytochemical investigation of Piper umbellata leaves yielded nine compounds including one terpenoid glucoside, five flavones (vitexin 2"-O-β-glucopyranoside, apigenin 8-C-β-D-glucopyranoside,orientin 8-C-β-D-glucopyranoside,5-hydroxy-7,3',4'-trimethoxy-flavone and velutin), two lignans (sesamin e dihydrocubebin) and 4-nerolidylcathecol. Excepting 4-nerolidylcathecol, all compounds have not been described from this species yet.

The phytochemical investigation of the flowers of Pterogyne nitens (Caesalpinioideae) resulted in the isolation and identification of nine phenolic derivatives, quercetin 3-O-sophoroside, taxifolin, astilbin, ourateacatechin, caffeic, ferulic, sinapic, chlorogenic and gallic acid, besides two guanidine alkaloids, pterogynine, pterogynidine. This is the first time these compounds have been reported in P. nitens flowers. As this is a monospecific genus, these secondary metabolites may have taxonomical significance. Their structures were assigned on the basis of spectroscopic analyses, including two-dimensional NMR techniques.

Espécies Reativas do Oxigênio (ERO) e radicais livres têm tido implicações na iniciação e evolução de muitas doenças ou nas causas das mesmas em organismos vivos; há portanto, necessidade contínua por moléculas antioxidantes para inativar ERO/radicais livres. Estudos sobre extratos brutos de plantas têm demonstrado suas ações antioxidante e seqüestradora de radicais livres. Espécies do gênero Maytenus são utilizadas, em vários países, como medicamentos tradicionais no combate a úlceras gástricas, dispepsia e outras desordens gástricas, bem como por suas propriedades antiinflamatórias. Neste estudo, o extrato bruto etanólico da raiz da Maytenus aquifolium (Celastraceae) foi avaliado quanto à sua habilidade em seqüestrar radicais livres e outras espécies reativas do oxigênio. Os resultados são expressos como porcentagem de inibição das espécies ativas. O extrato foi eficiente contra as espécies estudadas: radical DPPH (inibição alcançada = 35,5 ± 1,3 %), ABTS•+ (IC50 = 0,0036 ± 0,0003 mg/mL), HOCl (IC50 = 0,002 ± 0,0001 mg/mL ), O2•- (inibição alcançada = 36,0 ± 2,1 %), and NO· (inibição alcançada = 18,3 ± 0,4 %).

Reactive oxygen species (ROS) and free radical species have been implicated in initiating, accompanying or causing many diseases in living organisms; there is thus, a continual need for antioxidants molecules to inactivate ROS/free radicals. Many studies of plants crude extracts have demonstrated free-radical scavenging and antioxidant action. Maytenus species have long been used, in several countries, as traditional medicines against gastric ulcers, dyspepsia and others gastric problems and for their anti-inflammatory properties. In this study, Maytenus aquifolium (Celastraceae) root bark ethanol extract was assessed for its ability to scavenge free radicals and reactive oxygen species. The results were expressed as percentage inhibition of the active species. The extract was efficient against studied reactive species: DPPH radical (obtained inhibition = 35.5 ± 1.3 %), ABTS•+ (IC50 = 0.0036 ± 0.0003 mg/mL), HOCl (IC50 = 0.002 ± 0.0001 mg/mL ), O2•- (obtained inhibition = 36.0 ± 2.1 %), and NO• (obtained inhibition = 18.3 ± 0.4 %).

Chromatographic fractionation of the organic extract from leaves of Ouratea multiflora afforded the flavone dimers heveaflavone, amentoflavone-7<FONT FACE=Symbol>¢¢</FONT>,4<FONT FACE=Symbol>¢¢¢</FONT>-dimethyl eter, podocarpusflavone-A and amentoflavone. Their structures were elucidated from spectral data, including 2D-NMR experiments of the natural substances. Biological activities of all isolates were evaluated, using antimicrobial assay against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, cytotoxicity assay against mouse lymphoma (L5178) and KB cell lines, TLC screening for acetylcholinesterase inhibitors and antioxidant activity measured by DPPH test.

O fracionamento cromatográfico do extrato orgânico das folhas de Ouratea multiflora forneceu os flavonóides diméricos, heveaflavona, 7<FONT FACE=Symbol>¢¢</FONT>,4<FONT FACE=Symbol>¢¢¢</FONT>-dimetilamentoflavona, podocarpusflavona-A e amentoflavona. Suas estruturas foram elucidadas com base nos dados espectrais, incluindo experimentos bidimensionais de RMN, das substâncias naturais. A atividade antibiótica de todos os isolados foi avaliada, usando-se as bacterias Gram-positivas Staphylococcus aureus and Bacillus subtilis. Teste de citotoxicidade nas linhagens de linfoma de ratos (L5178) e KB também foram conduzidos para avaliar os extratos e os flavonóides isolados. a triagem biológica para a avaliação de atividade antioxidante e inibidora de acetil colinesterase foram conduzidas pela técnica da bioautografia com DPPH e teste pelo teste de Ellman respectivamente.

Estudos metabólicos envolvendo a incorporação de D-glicose-[1-13C] em folhas de Piper aduncum (Piperaceae) mostraram que as vias do mevalonato (MVA) e da triose-piruvato (MEP) estão envolvidas na biossíntese da unidade isoprênica presente no 2,2-dimetil-2H-1-cromeno-6-carboxilato de metila (1) e no 2,2-dimetil-8-(3'-metil-2'-butenil)-2H-1-cromeno-6-carboxilato de metila (2). O padrão de incorporação dos carbonos marcados com D-glicose-[1-13C] destes cromenos foram determinados através de espectroscopia de RMN de 13C quantitativo. Os resultados confirmaram que o compartimento biossintético de 1 e 2 pode ser o plastídio e/ou citosol, ou possivelmente um compartimento adicional, como o espaço entre a membrana e o plastídio.

Metabolic studies involving the incorporation of [1-13C]-D-glucose into intact leaves of Piper aduncum (Piperaceae) have indicated that both the mevalonate (MVA) and the pyruvate-triose (MEP) non-mevalonate pathways are implicated in the biosynthesis of isoprene moieties present in methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (1) and methyl 2,2-dimethyl-8-(3'-methyl-2'-butenyl)-2H-1-chromene-6-carboxylate (2). The pattern of incorporation of label from [1-13C]-D-glucose into these chromenes was determined by quantitative 13C NMR spectroscopy. The results confirmed that biosynthetic compartment of 1 and 2 could either be the plastid and/or the cytosol or, possibly, an additional compartment such as the plastid inter-membrane space.