The roots of Solanum paniculatum (Solanaceae) have extensively been used in folk medicine to treat liver infections and as a diuretic. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) were used for the profiling and structural characterization of alkaloids from the roots of S. paniculatum. Sixteen 3-aminofurostane alkaloids were characterized as novel compounds. In this study, three principal alkaloids were isolated in mixture, and their structures were established by different spectroscopic methods, including 1D, 2D nuclear magnetic resonance (NMR) experiments, and the high-resolution electrospray ionization (HR-ESI)-MS analysis. The isolated alkaloids were used to explore fragmentation pathways. Compound identification was based on the exact mass and fragmentation behaviors. Two compounds were identified as new natural compounds as: (25R)-3β-amino-furost-5-en-22α,26-diol O(26)-β-D-glucopyranoside (fatimagraine) and (25R)-3β-amino-furost-22-en,26-ol O(26)-β-D-glucopyranoside (bhattacharyyaine). The unambiguous assignments of 1H and 13C NMR data and chemical correction of the structure alkaloid jurubine are reported for the first time.

Melissopalynological, physicochemical analysis, mineral content, antiradical activity and profile of compounds by Ultra-Performance Liquid Chromatography coupled with a Diode Array Detector and quadrupole Time of Flight Mass Spectrometry (UPLC-DAD-qTOF-MS/MS) of Frieseomelitta doederleini honeys from semiarid region of the Northeast of Brazil are presented. The melissopalynological analysis showed two principal pollen types of Mimosa tenuiflora (jurema preta) and Shinus sp (aroeira). The chemical profile data obtained by UPLC-DAD-qTOF-MS/MS of the Mimosa tenuiflora flowers (principal pollen of honey) and the five samples of F. doederleini honeys both flowers and honey showed similar profile. Abelha branca honeys samples had similar characteristic profile of phenolic compounds (flavonoids), and also antiradical activity. The main flavonoids identified in the honey samples in the jurema preta flowers were flavonols/flavone and flavanols/flavanones aglycones. All the flavonoids identified showing that the nectar collected by the bees may be from this plant species. The antiradical activity of the honey samples strongly correlated with their phenolic content. Among the minerals analyzed, potassium was the most abundant, followed by magnesium.

A modified and efficient Knoevenagel condensation procedure was developed to synthesize the title compounds using β-alanine and acetic acid as catalysts, showing good to excellent yields. We used lawsone with suitable aliphatic aldehydes including isobutyraldehyde, 3-methyl-butyraldehyde, 2-ethylbutyraldehyde, phenylacetaldehyde, 2-phenyl-propionaldehyde, among others. These compounds were submitted to cytotoxic screening against three tumor cell lines presenting good to excellent cytotoxic profiles.

The aim of this investigation was to analyze two samples of pollen collected by Apis mellifera bees in view of their chemical composition, antiradicalar and antimicrobial activities. Palynological analysis showed that the predominant pollen was Fabaceae species (42.3%, sample I and 50.6%, sample II). The characterization by ultra-performance liquid chromatography coupled with a diode array detector and quadrupole time of flight mass spectrometry (UPLC-DAD-QTOF-MS/MS) resulted in the identification of three derivatives of putrescine (di-4-coumaroylputrescine, coumaroyl-feruloyl-putrescine and di-feruloyl-putrescine), two spermidine derivatives (coumaroyl-di-cafeoyl-spermidine and tri-coumaroyl-spermidine and four biflavonoids (2,3-di-hydrohydroxy-amentoflavone, 2,3-dihydro-amentoflavone, amentoflavone and 2,3-dihydro-biapigenin). The two samples showed antiradical and antimicrobial activities, probably due to the presence of these compounds.

Halogenated compounds are valuable substrates for the field of organic synthesis and more specifically as reagents for coupling reactions. Environmental friendly procedures for regioselective iodination is the aim of this study, using four different methods previously described in the literature, that embrace green chemistry concepts, to obtain the 6- and 8-iodo-isomers of 3,7,3’,4’-tetramethoxy-quercetin. As traditional column chromatography does not resolve the mixture of isomers, the regioselectivity for iodination was quantified by use of HPLC. The use of a protic polar solvent improves selectivity for formation of the 8-iodo- isomers (tipically, I2, LiOH, MeOH, 3 h, 54% yield), while the use of a polar aprotic solvent or in the absence of a solvent favors formation of the 6-iodo- isomer (typically, I2, K2CO3, without solvent, 5 min, 60% yield). Twenty-one reaction procedures were investigated, five of which selectively gave the 6,8-diiodo-derivative. To the best of our knowledge, selective methods for the synthesis of this compound have not been described in the literature. The best condition was the neat reaction with N-iodo-succinimide with 68% yield in just a few minutes. All product yields are after column chromatography using silica gel, and characterized by usual methods, including 1H-NMR, 13C-NMR, IR and MS-TOF.

Click chemistry-based strategies for the synthesis of 2-amino-alkyl-1,2,3-triazole-1,4-naphthoquinone derivatives make it possible to obtain desired products from 1,4-naphthoquinone (1,4-NQ), and bio-based lawsone, nor-lapachol and lapachol. The first route (Strategy A) starting from 1,4-NQ and amino alcohols, then 2-amino-alkyl-1,4-NQ alcohols, were tosylated. The azide ion displaced the tosylate group to afford 2-azide-alkyl-1,4-NQ, which was submitted to a copper-catalyzed azide alkyne cycloaddition (CuAAC) condition. The triazole-naphthoquinones were obtained in an overall yield of roughly 47%. Another pathway (Strategy B) substituted bromo-alkyl-phthalimides using NaN3 as the nucleophile, sequential CuAAC and deprotection of phthalimide group with hydrazine producing amino-triazoles. The subsequent reaction with 1,4-NQ produced 2-amino-alkyl-1,2,3-triazole-1,4-NQ derivatives in an overall yield of 45-76% in four steps. After we developed these two strategies, linear synthesis (Strategy A) was chosen to prepare 2-[(2-(1H-1,2,3-triazol-1-yl)ethylamino)]-3-(3-methylpropenyl)-1,4-naphthoquinones from lawsone with an overall yield of approximately 27% in six steps. On the other hand, convergent synthesis (Strategy B) was employed for the synthesis of 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)alkyl-amino)]-3-(3-methylbut-2-en-1-yl)-1,4-naphthoquinones from the reaction between 2-methoxy-lapachol with amino-triazoles with a global yield of about 21%. These synthetic strategies might lead us to new opportunities to build small-molecule libraries for future biological exploration.

ABSTRACT Hyptis pectinata (L.) Poit., Lamiaceae, popularly known as "sambacaitá," is an aromatic shrub largely grown in the Brazilian northeastern. We investigated the antinociceptive effects of the ethyl acetate fraction obtained from the leaves of H. pectinata and of its main constituent rosmarinic acid, on formalin (2%)-, glutamate (25 µM)- and capsaicin (2.5 µg)-induced orofacial nociception in rodents. Male mice were pretreated with ethyl acetate fraction (100, 200 or 400 mg/kg, p.o.), rosmarinic acid (10 or 20 mg/kg, p.o.), morphine (5 mg/kg, i.p.), or vehicle (distilled water + 0.2% Tween 80). Ethyl acetate fraction reduced the nociceptive face-rubbing behavior during the two phase of the formalin test, whereas pretreatment with rosmarinic acid decreased the pain behavior in the second phase. Ethyl acetate fraction produced significant antinociceptive effects in the capsaicin and glutamate tests. This study showed that oral administration of ethyl acetate fraction produced potent antinociceptive effects compared to treatment with rosmarinic acid.

A convenient, efficient and fast acetylation combining clays and ultrasound irradiation is described. Some molecules from nature or synthetic source, i.e., D-glucose, glycerol, D-mannitol and 1,2,3-triazolic derivatives such as N-glucosyl sugars and 2-substituted 1,4-naphthoquinone structures were acetylated. This kind of chemistry may be classified as eco-friendly because the reactions take a short time and the catalyst is reusable.

Uma série de derivados 2,3-diino-1,4-naftoquinona foi sintetizada a partir do 2,3-dibromo1,4-naftoquinona e diversos alquinos terminais funcionalizados usando a reação de acoplamento de Sonogashira catalisada por paládio. Os compostos foram submetidos à avaliação do potencial citotóxico em três linhagens de células tumorais, OVCAR-8 (ovário), PC-3M (próstata) e NCI-H358M (pulmão), apresentando, no geral, resultados satisfatórios para inibição do crescimento celular.

A series of 2,3-diyne-1,4-naphthoquinone derivatives was synthesized from 2,3-dibromo1,4-naphthoquinone and various functionalized terminal alkynes using palladium-catalyzed Sonogashira cross-coupling reaction. The diynes were evaluated as potential cytotoxic agents against three tumor cell lines: human ovarian adenocarcinoma (OVCAR-8), human metastatic prostate cancer (PC-3M) and human bronchoalveolar lung carcinoma (NCI-H358M), presenting, in general, satisfactory results for inhibition of cell growth.

Uma série de derivados 1,2,3-triazólicos foi sintetizada a partir de N-alquilftalimida-azidas (A1 -A4) e alcinos (a-e) sob irradiação de ultrassom na presença de CuI, Et3N e DMF como solvente. O presente protocolo forneceu 18 novos 1,2,3-triazóis (1-4) em rendimentos de bons a excelentes (67-98%).

A series of 1,2,3-triazole derivatives was synthesized from N-phthalimidoalkyl-azides (A1 -A4) and alkynes (a-e) under ultrasound irradiation in the presence of CuI, Et3N and DMF as solvent. The present protocol afforded 18 new 1,2,3-triazoles (1-4) in good-to-excellent yields (67-98%).

A reação do lapachol à temperatura ambiente, com aminas alifáticas primárias forneceu novos adutos identificados como derivados do núcleo fenazina. Os produtos foram obtidos em rendimentos bons a razoáveis (52 a 88%), a temperatura ambiente e sem o uso de solvente, a partir da reação com alquilaminas funcionalizadas, como n-butilamina, etanolamina, 3-propanolamina, 2-metoxi-etilamina, 3-metoxi-propilamina e 2-feniletilamina.

New adducts of lapachol with neat primary aliphatic amines were obtained in a solvent-free reaction in good to reasonable yields (52 to 88%), at room temperature. The new compounds containing a phenazine moiety were obtained from suitable functionalized aminoalkyl compounds, including ethanolamine, 3-propanolamine, 2-methoxy-ethylamine, 3-methoxy-propylamine, n-butylamine and 2-phenetylamine.

As abelhas sem ferrão são espécies indígenas encontradas em todo o Brasil. Seu pólen é utilizado devido ao seu valor nutricional na dieta humana. É produzido a partir de pólen floral misturado com néctar e líquidos secretados pelas abelhas. Visando avaliar a composição química, a atividade sequestradora de radicais livres e a origem botânica foi estudado o pólencoletado pela abelha sem ferrão Melipona rufiventris (Uruçu-amarela). Do extrato acetato de etila foram isolados os compostos: ácido phidroxicinâmico, dihidroquercetina, isoramnetina, 3O(6"OEpcoumaroil)βDglicopiranosideoisoramnetina, luteolina e quercetina. Esta é a primeira vez que a 3O(6"OEpcoumaroil)βDglicopiranosideoisoramnetina é isolada de pólen apícola. A atividade sequestradora de radicais livres de vários extratos com solventes diferentes foi determinada pelo teste com DPPH (difenilpicrilhidrazida). A atividade mostrou a ordem decrescente para os extratos AcOEt>EtOH>Hexano. O extrato AcOEt apresenta melhor atividade sequestradora de radicais. A avaliação botânica palinológicamostrou que o pólen era composto de dois tipos, um majoritário(97.3%) proveniente de Scoparia dulcis (L.) (Scrophulariaceae) e outro minoritário proveniente de Senna obtusifolia (L.) Irwin& Barneby (Fabaceae). Estes resultados sugerem o comportamento de forragem bastante específico exibido pela abelha Melipona rufiventris, mesmo em um ambiente tão rico em diversidade vegetal como o Nordeste do Brasil.

Stingless bees in Brazil are indigenous and found all over the country. Bee pollen is used for its nutritional value in the human diet. It is made up of natural flower pollen mixed with nectar and bee secretions. In order to evaluate the chemical composition, free radical scavenging activity, and botanical origin, sample of pollen loads from stingless bee, Melipona rufiventris (Uruçu amarela) was studied. The EtOAc extract of pollen of Melipona rufiventris yielded the following compounds: p-hydroxycinnamic acid, dihydroquercetin, isorhamnetin, isorhamnetin3-O-(6"-O-E-p-coumaroyl)-β-D-glucopyranoside, luteolin, and quercetin. This is the first report of the isolation of isorhamnetin3-O-(6"O-E-p-coumaroyl)β-D-glucopyranoside from pollen. The free radicalscavenging activities of different solvent extracts of pollen were determined using DPPH assay. This activity decreases in the order: EtOAc>EtOH>Hexane extract. It appears that the EtOAc extract of the pollen is a good scavenger of active oxygen species. The botanical evaluation of pollen loads showed the composition by two pollen types, with the dominant type (97.3%) being Scopariadulcis (L.) (Scrophulariaceae) and the minor one Senna obtusifolia (L.) Irwin & Barneby (Fabaceae). This suggests a specific foraging behavior in Melipona rufiventris bees, even in an environment with such a rich botanical diversity as the Northeastern Brazil.

A reação do flavonol 3,7,3',4'-tetra-O-metilquercetina (1) e da isoflavona 7,4'-di-O-metilgenisteina (2) com iodo/KOH em metanol forneceu como produto quatro derivados iodados: 8-iodo-5-hidroxi-3,7,3',4'-tetrametoxiflavona (1a) e 6-iodo-5-hidroxi-3,7,3',4'-tetrametoxiflavona (1b) a partir da iodação de 1; a partir de 2 foi obtida uma mistura racêmica composta de (±)-trans-5-hidroxi-2,3,7,4'-tetrametoxi-8-iodo-isoflavanona (2a) e (±)-trans-5-hidroxi-2,3,7,4'-tetrametoxi-6,8-diiodo-isoflavanona (2b). A formação destes diferentes produtos revela a significante diferença envolvendo a interação química entre o sitio reativo de cetonas α, β-insaturadas de flavonol e de isoflavonas nas condições experimentais testadas (usando I2/KOH/MeOH). Além disso, ressalta-se a estereosseletividade trans na adição de metanol ao sistema α, β-insaturado da isoflavona. As estruturas foram identificadas com análise nos dados espectrométricos de RMN 1D e 2D e massas.

The reaction of the flavonol 3,7,3', 4'-tetra-O-methylquercetin (1) and of the isoflavone 7,4'-di-O-methylgenistein (2) with alkaline iodine in methanol afforded four new iodine derivatives: 8-iodo-5-hydroxy-3,7,3', 4'-tetramethoxy- flavone (1a) and 6-iodo-5-hydroxy-3,7,3', 4'-tetramethoxyflavone (1b) from 1; 2 afforded a mixture of two compounds, identified as a racemic mixture of (±)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-8-iodo-isoflavanone (2a) and (±)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-6,8-diiodo-isoflavanone (2b). The formation of these different products reveals a significant difference involving the chemical interaction between the reactive site of α, β-unsaturated ketones of flavonol and isoflavone under the tested reaction conditions (using I2/KOH/MeOH). Furthermore, the trans stereo selectivity is noteworthy in the nucleophylic addition of methanol at the isoflavone α, β-unsaturated system. The structures were identified on the basis of spectral data, mainly 1D and 2D NMR and mass spectra.

A toxicidade da lausona (2-hidroxi-1,4)-naftoquinona e de diversos derivados foi avaliada frente à Artemia salina e ao molusco Biomphalaria glabrata, o principal vetor de transmissão da esquistossomose no Brasil. Entre os dezessete compostos testados, nove apresentaram um perfil de toxicidade menor que 100 µg/mL, sendo potenciais agentes moluscicidas de acordo com as designações da Organização Mundial da Saúde. No presente estudo, os compostos contendo substituintes apolares exibiram as maiores atividades. Estes compostos também se mostraram significantemente tóxicos frente à A. salina.

The toxic profile of lawsone (2-hydroxy-[1,4]naphthoquinone) and a series of [1,4]naphthoquinone derivatives was evaluated against the brine shrimp Artemia salina and against the mollusk Biomphalaria glabrata, the main transmitting vector of schistosomiasis in Brazil. Of the seventeen compounds tested nine fell below the threshold of 100 µg/mL set for potential molluscicidal activity by the World Health Organization. As a general rule derivatives with non-polar substituents presented the highest molluscicidal activities. These substances showed significant toxicity in A. salina lethality bioassay.

O lapachol, α e β-lapachona são naftoquinonas obtidas de espécies de Tabebuia, apresentam propriedades antiinflamatória, antibacteriana, anticâncer e tripanossomicida. O objetivo deste trabalho foi investigar um possível efeito espasmolítico destas naftoquinonas em íleo de cobaia, uma vez que, outras naftoquinonas inibem a atividade contrátil de músculos lisos. O lapachol, α e β-lapachona inibiram as contrações fásicas induzidas tanto por carbacol (CI50 = 1,5 ± 0,2 x 10-4; 7,3 ± 0,9 x 10-5 e 3,2 ± 0,5 x 10-5 M, respectivamente) quanto por histamina (CI50 = 3,6± 0,5; 3,6 ± 0,7 e 3,3 ± 0,6 x 10-5 M, respectivamente). Estes compostos também relaxaram o íleo pré-contraído com KCl (CE50 = 1,2 ± 0,4; 4,3 ± 0,8 e 2,7 ± 0,2 x 10-5 M, respectivamente); carbacol (CE50 = 2,6 ± 0,7; 3,5 ± 0,5 e 2,2 ± 0,7 x 10-5 M, respectivamente) ou histamina (CE50 = 3,0 ± 0,8; 1,1 ± 0,3 e 3,3 ± 0,6 x 10-5 M, respectivamente) de maneira dependente de concentração. Este efeito é provavelmente devido à inibição do influxo de Ca2+ através dos canais de Ca2+ dependentes de voltagem (CaV). β-lapachona antagonizou (pD'2 = 5,73 ± 0,12; "slope" = 1,51 ± 0,05) as contrações induzidas por CaCl2 em meio despolarizante nominalmente sem Ca2+. O achado de que a β-lapachona inibiu as contrações tônicas induzidas por S-(-)-Bay K8644 (CE50 = 1,4 ± 0,1 x 10-5 M) é sugestivo que o CaV envolvido é o do tipo L. Em conclusão, lapachol, α e β-lapachona apresentam atividade espasmolítica não seletiva em íleo de cobaia, e β-lapachona exerce este efeito pelo bloqueio dos canais CaV tipo L.

Lapachol, α and β-lapachone are naphthoquinones extracted from species of Tabebuia that have shown antiinflammatory, antibacterial, anticancer and trypanosomicidal properties. The aim of this work was to investigate the spasmolytic effect of these naphthoquinones on the guinea-pig ileum, since other naphthoquinones are known to depress the contractile activity of smooth muscles. Lapachol, α and β-lapachone inhibited the phasic contractions induced by both carbachol (IC50 = 1.5 ± 0.2 x 10-4; 7.3 ± 0.9 x 10-5 and 3.2 ± 0.5 x 10-5 M, respectively) and histamine (IC50 = 3.6± 0.5; 3.6 ± 0.7 and 3.3 ± 0.6 x 10-5 M, respectively). These compounds also relaxed the ileum pre-contracted with KCl (EC50 = 1.2 ± 0.4; 4.3 ± 0.8 and 2.7 ± 0.2 x 10-5 M, respectively); carbachol (EC50 = 2.6 ± 0.7; 3.5 ± 0.5 and 2.2 ± 0.7 x 10-5 M, respectively) or histamine (EC50 = 3.0 ± 0.8; 1.1 ± 0.3 and 3.3 ± 0.6 x 10-5 M, respectively) in a concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-gated calcium channels (Ca v). β-lapachone antagonized (pD'2 = 5.73 ± 0.12; slope = 1.51 ± 0.05) CaCl2-induced contractions in depolarizing medium nominally without Ca2+. The finding that β-lapachone inhibited the tonic contractions induced by S-(-)-Bay K8644 (EC50 = 1.4 ± 0.1 x 10-5 M) is suggestive that the L-type CaV is involved. In conclusion, lapachol, α and β-lapachone showed non-selective spasmolytic activity in guinea-pig ileum, and β-lapachone exerts this effect by to blockade of L-type CaV channels.