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Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents.
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Biomarcadores , Estresse Oxidativo , Extratos Vegetais , Ratos Wistar , Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Masculino , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Glutationa Peroxidase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Fusarium graminearum causes destructive ear rot diseases in maize and wheat. New antifungals are essential to combat this pathogen, and aerial parts of Justicia species (Acanthaceae) are a potential source. We investigated the antifungal activity of extracts from stems and leaves of five Justicia species native to Northwest Argentina. The aerial parts were subjected to sequential extractions with dichloromethane, ethyl acetate, and methanol. The resulting extracts were tested by the disc diffusion method against F. graminearum strains. Only the leaf and stem extracts from J. xylosteoides displayed inhibitory effects, with the dichloromethane leaf extract as the most active. The compounds involved were identified as the lignans hinokinin, savinin, and isohibalactone. Both the dichloromethane extract and hinokinin synergised with tebuconazole, and inhibited deoxynivalenol biosynthesis. The identified compounds warrant further research as additives to azole fungicides for F. graminearum control.
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The hexane extract from twigs of Piper truncatum Vell (Piperaceae) displayed activity against Trypanosoma cruzi and was subjected to chromatographic steps to afford six dibenzylbutyrolactolic lignans, being four knowns: cubebin (1), (-)-9α-O-methylcubebin (2), (+)-9ß-O-methylcubebinin (3) and 3,4-dimethoxy-3,4-demethylenedioxycubebin (4) as well as two new, named truncatin A (5) and B (6). Initially, inâ vitro activity against trypomastigotes was evaluated and compounds 1, 4 and 6 exhibited EC50 values of 41.6, 21.0 and 39.6â µM, respectively. However, when tested against amastigotes, the relevant clinical form in the chronic phase of Chagas disease, compounds 1-6 displayed activities with EC50 values ranging from 1.6 to 13.7â µM. In addition, the mammalian cytotoxicity of compounds 1-6 was evaluated against murine fibroblasts (NCTC). Compounds 2, 3 and 4 exhibited reduced toxicity against NCTC cells (CC50>200â µM), resulting in SI values of>21.9,>14.5 and>121.9, respectively. Compound 4 showed the highest potency with an SI value twice superior to that determined by the standard drug benznidazole (SI>54.6) against the intracellular amastigotes. These data suggest that lignan 4 can be considered a possible scaffold for designing a new drug candidate for Chagas disease.
Assuntos
Lignanas , Piper , Tripanossomicidas , Trypanosoma cruzi , Lignanas/farmacologia , Lignanas/química , Lignanas/isolamento & purificação , Piper/química , Animais , Trypanosoma cruzi/efeitos dos fármacos , Camundongos , Tripanossomicidas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação , Relação Estrutura-Atividade , Testes de Sensibilidade Parasitária , Fibroblastos/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacosRESUMO
In vitro larvicidal assays carried out previously by our research group with cubebin, dihydrocubebin and hinokinin, lignans extracted from the fruits of Piper cubeba, against Haemonchus contortus larvae showed strong action larvicidal these compounds. Hinokinin was the most active (EC50 = 0.34 µg/mL) with strong action on the cuticle of the larvae as observed by scanning electron microscopy of the L3 stage. Therefore, to understand the mechanism of action of these compounds in silico studies were carried out using the enzyme phosphomethyltransferase of Haemonchus contortus that contain PMT-1 and PMT-2 di-domains responsible for phosphocholine synthesis, which is one of the main lipids in nematodes. This pathway is not found in mammals, so this enzyme is an important biological target for the development of new anthelmintics. Results of molecular docking, molecular dynamic and a density functional theory calculations studies with the three lignans show few interactions with PMT-1. However, hinokinin has important interactions with PMT-2, that can deactivate the enzyme and interrupt the phosphocholine synthesis, which is an essential compound for the development and maintenance of the nematode cuticle and its survive. Therefore, the previous results of the in vitro assay allied with in silico results, now realized; suggest that hinokinin may be a possible selective target for the development of new anthelmintics against Haemonchus contortus since the PMT-2 domain is present in this nematode.
Assuntos
Anti-Helmínticos , Haemonchus , Lignanas , Nematoides , Piper , Animais , Simulação de Acoplamento Molecular , Fosforilcolina/farmacologia , Lignanas/farmacologia , Anti-Helmínticos/farmacologia , Larva , MamíferosRESUMO
Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. To do so, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epidermal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), serine/threonine-protein kinase mTOR (mTOR) and poly [ADP-ribose] polymerase-1 (PARP1). Then, single nucleotide polymorphisms were mapped, target mutations were designed, and molecular docking was performed with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.
Assuntos
Perfil Genético , Lignanas , Simulação de Acoplamento Molecular , Histona Desacetilases , Lignanas/farmacologia , Serina-Treonina Quinases TORRESUMO
The Pipercubeba, it is one spice, widely consumed in Europe, which has several bioactive molecules, between those a lignan named cubebin. Cubebin has several known biological activities, such as analgesic activity and anti-inflammatory, trypanocidal activity, leishmanicidal and antitumor activity. The objective of this study was to evaluate the antiproliferative activity "in vitro" cubebin in eight different human tumor cell lines. It was fully characterized by IR analysis, NMR, mass spectrometry, DSC, TGA, residual solvent and elemental analysis. The antitumor activity of cubebin was evaluated "in vitro" on eight different human tumor cell lineages. Cubebin showed GI50≤30µg/mL for lineage cell U251 (glioma CNS), 786-0 (kidney), PC-3 (prostate), HT-29 (colon rectum). For K562 cells (leukemia), cubebin presented GI50≤to 4.0mg/mL. For the other lineages cells, MCF-7 (breast) and NCI-H460 to cubebin can be considered inactive because of GI50>250mg/mL. Analyzing the selectivity index for cubebin, it can be observed that high selectivity of cubebin to K562 lineage cells (leukemia). Analyzing the cytotoxic potential of cubebin was observed that probably acts cubebin altering metabolism, inhibiting cell growth - a cytostatic effect, showing no cytocidal effect on any lineage cell.
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Artemisia cina is a plant used in traditional Chinese medicine as a remedy for parasitic diseases. This study describes the isolation and chemical characterization of anthelmintic compounds of A. cina against Haemonchus contortus infective larvae (L3) through lethal testing. Previously, three extracts-n-hexane (HexAc), ethyl acetate (EtOAc) and methanol (MeOAc)-were evaluated at concentrations of 4 to 0.5 mg/mL, resulting in the HexAc extract with the greatest effect of 76.6% mortality of the larvae at 4 mg/mL. Then, this was chemically fractioned by polarity, obtaining seven fractions (C1F1-C1F7), and, when evaluated at concentrations from 2 to 0.25 mg/mL, the 2 mg/mL C1F5 fraction produced an effect against the nematode H. contortus of 100% mortality of the larvae. Thus, this fraction was fractionated again by column chromatography, obtaining twelve subfractions (C2F1-C2F12) which were evaluated from 1 to 0.125 mg/mL, with the C2F5 subfraction causing a nematicidal effect of 100% mortality. NMR analysis of one (1H, 13C and DEPT) and two dimensions (COSY, HSQC and HMBC) and mass spectrometry of this fraction allowed us to identify the mixture of 3'-demethoxy-6-O-demethylisoguaiacin and norisoguaiacin. Therefore, it can be assumed that the mixture of these compounds is responsible for the anthelmintic effect. These results indicate that A. cina containing anthelmintic compounds and might be used as an antiparasitic drug against H. contortus.
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Aedes aegypti is the primary vector of virus transmission that causes dengue, yellow fever, chikungunya and zika. The primary prevention method has been vector control and synthetic insecticides that can cause environmental side effects. Thus, the work aimed to evaluate the larvicidal potential of extracts and isolated compounds from Piper cubeba against A. aegypti larvae. The larvicidal activity method was executed according to the World Health Organization protocol. The larvae were analyzed by scanning electron microscopy (SEM). Through molecular docking, the action mechanism was investigated. The hydroalcoholic and hexane extracts showed similar larvicidal activity with LC50 of 191.1 µg/mL and 185.84 µg/mL, respectively. Between isolated compounds, hinokinin presented LC50= 97.74 µg/mL. The SEM analysis showed structural damage to the larva's tegument caused by extracts and isolated compounds. Therefore, the results demonstrate the larvicidal action of hinokinin and extracts, which can lead to the development of new natural larvicides.
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Assessing the dietary intake of polyphenols and their major food sources is the first step towards documenting the associations with health outcomes. Considering recent changes in dietary patterns of the Brazilian population, continuous monitoring of polyphenol intake is important. Thus, the present study was conducted to estimate the polyphenol intake and major food sources in the diet of the Brazilian population using data from the most recent National Dietary Survey (NDS, 2017-2018), to characterise the intake changes according to demographic characteristics and to compare the intake over the past decade in Brazil. Data from two cross-sectional population-based surveys were analyzed in the study. Trends in polyphenol intake and major food sources were estimated using food consumption data from NDS 2008-2009 (n 34 003) and 2017-2018 (n 46 164). The median (25-75th percentiles) of energy-adjusted polyphenol intake in 2017-2018 was 216·3 mg (125·3-495·2 mg) per 1000 kcal/d (4184 kJ/d), representing an increase of 12·3 mg/d from 2008-2009. However, unadjusted polyphenol intakes were similar between the surveys (medians: 364·3 mg/d in 2008-2009 and 366·9 mg/d in 2017-2018). The main food sources of total and polyphenol intake classes presented some variations between 2008-2009 and 2017-2018, with greater contribution of beans preparations, salads and tea to polyphenol intake, and decrease of orange contribution. Our study provided an updated information on polyphenol intake and its major food sources. The median intake remains lower than the reported by other populations. Furthermore, the results may contribute to future studies investigating temporal trends in polyphenol intake and disease risk.
Assuntos
Flavonoides , Polifenóis , Polifenóis/análise , Brasil , Fenóis/análise , Estudos Transversais , DietaRESUMO
The critical enzyme dihydrofolate reductase-thymidylate synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. Through consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in silico predictions were then validated through in vitro assays to examine the inhibitory capacity of the top-ranked naturally occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 µM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4'-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease.
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Asteraceae , Cinamatos , Leishmania major , Lignanas , Tetra-Hidrofolato Desidrogenase , Timidilato Sintase , Aprendizado de MáquinaRESUMO
Lignans, a group of polyphenols, have been identified in eight cold pressed oils from fruits, nuts, and seeds, retrieved from the Brazilian market. The oils under investigation were avocado, Brazilian nut, canola, coconut, grapeseed, macadamia, palm, and pequi. Olive oil was selected as a reference oil, since numerous data on its lignan content are available in literature. The qualitative and quantitative profiles were obtained, after extraction, by means of UFLC-ESI-MS/MS analyses. The total lignan content showed a high variability, ranging from 0.69 mg·Kg-1 (pequi) to 7.12 mg·Kg-1 (grapeseed), with the highest content registered for olive oil. Seven lignans were quantified, matairesinol and pinoresinol being the most abundant. The LC-MS/MS method was validated, showing linearity in the range of 12.5-212.5 mg·Kg-1, LOD in the range of 0.18-11.37 mg·Kg-1, and LOQ in the range of 0.53-34.45 mg·Kg-1. Additionally, part of the study was focused on the evaluation of the flavor profile, this being a key element in consumers' evaluations, by means of HS-SPME-GC. In total, 150 volatile compounds were determined in the eight oils, with identified fractions ranging from 91.85% (avocado) to 96.31% (canola), with an average value of 94.1%. Groups of components contributed characteristically to the flavour of each oil.
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The Piper species are a recognized botanical source of a broad structural diversity of lignans and its derivatives. For the first time, Piper tectoniifolium Kunth is presented as a promising natural source of the bioactive (-)-grandisin. Phytochemical analyses of extracts from its leaves, branches and inflorescences showed the presence of the target compound in large amounts, with leaf extracts found to contain up to 52.78% in its composition. A new HPLC-DAD-UV method was developed and validated to be selective for the identification of (-)-grandisin being sensitive, linear, precise, exact, robust and with a recovery above 90%. The absolute configuration of the molecule was determined by X-ray diffraction. Despite the identification of several enantiomers in plant extracts, the major isolated substance was characterized to be the (-)-grandisin enantiomer. In vascular reactivity tests, it was shown that the grandisin purified from botanical extracts presented an endothelium-dependent vasorelaxant effect with an IC50 of 9.8 ± 1.22 µM and around 80% relaxation at 30 µM. These results suggest that P. tectoniifolium has the potential to serve as a renewable source of grandisin on a large scale and the potential to serve as template for development of new drugs for vascular diseases with emphasis on disorders related to endothelial disfunction.
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Furanos/química , Lignanas/química , Piper/química , Extratos Vegetais/química , Furanos/metabolismo , Lignanas/metabolismo , Piper/metabolismoRESUMO
Two new tetrahydrofuran lignans 1-2, along with 2,3-seco-lup-20(29)-en-2,3-dioic acid (3), (-)-larreatricin (4), and 15 additional compounds were isolated from Combretum mellifluum (Combretaceae). Their structures were determined by 1D- and 2D- NMR spectroscopic data and HRESIMS. Another 15 compounds were identified after HPLC-DAD-MS/MS analysis. Tested against HT-29 (colon) neoplastic cells, lignan 1 showed marked cytotoxicity (GI50 = 3.9 µM) and high selectivity (SI > 227), compared with non-neoplastic NIH/3T3 cells, while 2 proved less cytotoxic, despite exhibiting SI > 75. Seco-triterpene 3 was strongly cytotoxic to 786-0 (kidney) and HT-29 cells (GI50 = 0.5 and 2.9 µM, respectively), proving roughly 107 and 18 times more selective for these cell lines, respectively, than for NIH/3T3 cells. After 48 h of incubation, 1-3 exhibited potent cytostatic activity against HT-29 cells at all concentrations tested, while 3 had a cytocidal effect on 786-0 cells at 25 µg.mL-1.
Assuntos
Combretum , Lignanas , Neoplasias , Triterpenos , Camundongos , Animais , Humanos , Combretum/química , Triterpenos/farmacologia , Triterpenos/química , Lignanas/farmacologia , Lignanas/química , Espectrometria de Massas em Tandem , Estrutura Molecular , Linhagem Celular TumoralRESUMO
OBJECTIVE: This study evaluated whether the consumption of a cereal bar combining different phytoestrogens could contribute to the reduction of climacteric symptoms in women. METHODS: This is a clinical, prospective, randomized, simple-blind trial. Forty-eight women, aged 40-65 years, with climacteric symptoms, from a city in southwestern Paraná, Brazil. Participants were randomly assigned into two groups; Phytoestrogens group (PHY = 24), which received for 90-day period a cereal bar containing 80.73 milligrams of soybean and flaxseed phytoestrogens, and the placebo group (PLA = 24), which consumed rice flakes biscuit. Clinical, sociodemographic and anthropometric data were collected and climacteric symptoms were assessed using the Kupperman Index (KI). RESULTS: Forty-three women were analyzed (PHY = 21 and PLA = 22). There were significant reductions in the overall KI score in both groups at the end of the intervention period (p < 0.05). However, the comparison between the groups using linear regression models presented expressively better symptom improvement in the PHY group -6.43 over time (95% CI: -11.6; -1.26; p < 0.05) KI points, with perimenopausal -15.15 (95% CI: -28.95; -1.35) and postmenopausal women -19.34 (95% CI: -33.68; -4.99) showed considerably greater reductions in symptoms at the end of the intervention period compared to premenopausal women. There was also significant reduction in symptoms of hot flushes, paresthesia, sexual complaints, insomnia and melancholy. CONCLUSION: The consumption of a cereal bar containing phytoestrogens was able to improve the symptoms of climacteric syndrome.
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Climatério , Isoflavonas , Grão Comestível , Feminino , Humanos , Isoflavonas/farmacologia , Fitoestrógenos/uso terapêutico , Poliésteres/farmacologia , Estudos ProspectivosRESUMO
Objective: This in vitro study evaluated the effect of neolignan-containing solutions on dentin biomodification previously applied to the bonding procedure in adhesive restorations. Material and Methods: Neolignans, dehydrodieugenol BCP1 and dehydrodieugenol B methyl etherCP2, were isolated from Nectandra leucanthaand two aqueous solutions containing 0.13% neolignans, 0.2% propylene glycol and 3.0% ethanol were prepared. Bovine teeth were ground flat to obtain 2-mm thick specimens which received resin composite restorations (N=10). The neolignan solutions were applied before the bonding procedure (60 s). Experimental groups were: control, untreated group, 0.12% chlorhexidine gel, 0.13% CP1 solution, and 0.13% CP2 solution. A push-out bond strength test was conducted (0.5 mm/min). Bovine tooth sections (0.5×1.7×7.0 mm) were also obtained to assess the modulus of elasticity and mass change after treatment (N=15). A three-point bending test evaluated the elastic modulus of fully demineralized dentine beams after immersion in the solutions. The data were statistically analyzed (α = 0.05). Results: The bond strength of the restorations to dentin was significantly improved by the treatment with neolignan-containing solutions, irrespective of the evaluation time (p<0.05). After 6 months, a significant reduction in the bond strength was observed in the groups treated with the solutions (p>0.05), but the means were significantly higher than the control groups (p<0.05). The elastic modulus of demineralized dentin was significantly improved after the treatment with the solutions (p<0.05). All groups lost mass weight. Conclusion: The solutions improved the in vitro longevity of bonded restorations, possibly due to the dentin biomodification effect of the neolignans.(AU)
Objetivo: Este estudo in vitro avaliou o efeito de soluções contendo neolignanas na biomodificação da dentina aplicadas previamente à restaurações adesivas. Material e Métodos: Neolignanas, desidrodieugenol BCP1 e éter metílico de desidrodieugenol B-CP2, foram isolados da espécie Nectandra leucantha e duas soluções aquosas contendo 0,13% de neolignanos, 0,2% de propilenoglicol e 3,0% de etanol foram preparadas. Dentes bovinos foram lixados para obter espécimes de 2 mm de espessura e preparos cavitários restaurados com resina composta (N=10). As soluções foram aplicadas em dentina antes do procedimento adesivo (60 s). Os grupos experimentais foram: controle, grupo não tratado, gel de clorexidina 0,12%, solução de CP1 a 0,13% e solução de CP2 a 0,13%. Foi realizado o teste de resistência de união push-out (0,5 mm/min). O módulo de elasticidade e a alteração de massa após tratamento da dentina (0,5×1,7×7,0 mm) foram também avaliados em teste de flexão de três pontos (N=15). Os dados foram analisados estatisticamente (α=0,05). Resultados: A resistência de união das restaurações à dentina melhorou significativamente com o tratamento com as soluções, independentemente do tempo de avaliação (p<0,05). Após 6 meses, foi observada redução significativa da resistência de união nos grupos tratados com as soluções (p>0,05), com médias significativamente maiores do que nos grupos controle (p<0,05). O módulo de elasticidade da dentina desmineralizada aumentou significativamente após tratamento com as soluções (p<0,05). Todos os grupos perderam massa, independentemente do tratamento. Conclusão: As soluções melhoraram in vitroa longevidade das restaurações adesivas, possivelmente devido ao efeito biomodificador da dentina das neolignanas(AU)
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Animais , Bovinos , Plantas Medicinais , Lignanas , Colágeno Tipo I , Restauração Dentária Permanente , DentinaRESUMO
Podophyllotoxins are natural lignans with known cytotoxic activity on several cell lines. The structural basis for their actions is mainly by the aryltetralin-lignan skeleton. Authors have proposed a cytotoxic mechanism of podophyllotoxins through the topoisomerase-II inhibition activity; however, several studies have also suggested that podophyllotoxins can inhibit the microtubules polymerization. In this work, the two possible mechanisms of action of two previously isolated compounds from the stem bark of Bursera fagaroides var. fagaroides: acetylpodophyllotoxin (1) and 5'-desmethoxydeoxypodophyllotoxin (2), was analyzed. An in vitro anti-tubulin epifluorescence on the MCF10A cell line and enzymatic topoisomerase II assays were performed. The binding affinities of compounds 1 and 2 in the colchicine binding site of tubulin by using rigid- and semiflexible-residues were calculated and compared using in silico docking methods. The two lignans were active by the in vitro anti-tubulin assay but could not inhibit TOP2 activity. In the in silico analysis, the binding modes of compounds into both rigid- and semiflexible-residues of tubulin were predicted, and only for the semiflexible docking method, a linear correlation between the dissociation constant and IC50 previously reported was found. Our results suggest that a simple semiflexible-residues modification in docking methods could provide an in vitro correlation when analyzing very structurally similar compounds.
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Lignanas/química , Podophyllum/toxicidade , Tubulina (Proteína)/metabolismo , Sítios de Ligação , Bursera/metabolismo , Bursera/fisiologia , Linhagem Celular Tumoral , Simulação por Computador , Humanos , Lignanas/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Podofilotoxina/farmacologia , Tubulina (Proteína)/efeitos dos fármacosRESUMO
Drimys winteri JR et G. Forster var chilensis (DC) A. is a tree native to central and southern Chile. Also it found in part of Argentina. It is abundant in wet swampy localities from sea level to an altitude of 1700 m. This tree is sacred for the Mapuche culture; it is used in folk medicine in such as inflammatory and painful processes. Phytochemical studies have demonstrated that this plant contains mainly sesquiterpenes of the drimane type, flavonoids, essential oils, phytosterols and some lignans. These drimanes have attracted interest because of their antifeedant, plant growth regulation, cytotoxic, antimicrobial and insecticidal properties. The objective of this review is to establish clearly the phytochemistry and biological activity of Drimys winteri JR et G. Forster var chilensis (DC) A. Articles based on other varieties are not considered.
Drimys winteri JR et G. Forster var chilensis (DC) A. es un árbol nativo del centro y sur de Chile. También se encuentra en parte de Argentina. Es abundante en localidades pantanosas y húmedas desde el nivel del mar hasta una altitud de 1700 m. Este árbol es sagrado para la cultura mapuche. Se utiliza en la medicina popular para tratar enfermedades como procesos inflamatorios y dolorosos. Los estudios fitoquímicos han demostrado que esta planta contiene principalmente sesquiterpenos del tipo drimano, flavonoides, aceites esenciales, fitoesteroles y algunos lignanos. Estos drimanos han despertado interés debido a sus propiedades antialimentarias, regulación del crecimiento de las plantas, propiedades citotóxicas, antimicrobianas e insecticidas. El objetivo de este examen es establecer claramente la fitoquímica y la actividad biológica de Drimys winteri JR et G. Forster var chilensis (DC) A. No se consideran los artículos basados en otras variedades D. winteri var winteri.
Assuntos
Óleos Voláteis/química , Drimys/química , Sesquiterpenos/análise , Flavonoides/análise , Lignanas/análiseRESUMO
Bursera fagaroides is a medicinal tree endemic to México, it belongs to the Burseraceae family and has proven antitumor activity. Modern research, performed principally with the bark extracts, have indicated that lignans are the main active constituents of B. fagaroides, with a high content of aryltetralin, aryldihydronaphtalene, dibenzylbutirolactone, and dibenzylbutane-type lignans as the constituents of the active extracts. In general, lignans from B. fagaroides exhibited potent anti-cancer activity, although antitumor, anti-bacterial, anti-protozoal, anti-inflammatory, and anti-viral properties have also been described. This review covers literature-reported lignans from B. fagaroides, chemical structures, nomenclature, chromatographic techniques of isolation, characterization strategies, and highlights the anti-cancer molecular mechanisms of lignans. Evaluation of the anticancer function of lignans has been extensively investigated since the cytotoxic in vitro results and in vivo assays in mice and zebrafish models to the tubulin molecular recognition by NMR. Also, we discuss the future direction for studying this important plant species and its lignan metabolites.
RESUMO
Seven phenolic compounds (ferulic acid, caffeic acid, 4-methoxycinnamic acid, 3,4-dimethoxycinnamic acid, 3-hydroxy-4-methoxybenzaldehyde, 3-methoxy-4-hydroxypropiophenone and 1-O,2-O-digalloyl-6-O-trans-p-coumaroyl-ß-D-glucopyranoside), a flavanonol (7-O-methylaromadendrin), two lignans (pinoresinol and matairesinol) and six diterpenic acids/alcohol (19-acetoxy-13-hydroxyabda-8(17),14-diene, totarol, 7-oxodehydroabietic acid, dehydroabietic acid, communic acid and isopimaric acid) were isolated from the hydroalcoholic extract of a Brazilian Brown Propolis and characterized by NMR spectral data analysis. The volatile fraction of brown propolis was characterized by CG-MS, composed mainly of monoterpenes and sesquiterpenes, being the major α-pinene (18.4 %) and ß-pinene (10.3 %). This propolis chemical profile indicates that Pinus spp., Eucalyptus spp. and Araucaria angustifolia might be its primary plants source. The brown propolis displayed significant activity against Plasmodium falciparum D6 and W2 strains with IC50 of 5.3 and 9.7â µg/mL, respectively. The volatile fraction was also active with IC50 of 22.5 and 41.8â µg/mL, respectively. Among the compounds, 1-O,2-O-digalloyl-6-O-trans-p-coumaroyl-ß-D-glucopyranoside showed IC50 of 3.1 and 1.0â µg/mL against D6 and W2 strains, respectively, while communic acid showed an IC50 of 4.0â µg/mL against W2 strain. Cytotoxicity was determined on four tumor cell lines (SK-MEL, KB, BT-549, and SK-OV-3) and two normal renal cell lines (LLC-PK1 and VERO). Matairesinol, 7-O-methylaromadendrin, and isopimaric acid showed an IC50 range of 1.8-0.78â µg/mL, 7.3-100â µg/mL, and 17-18â µg/mL, respectively, against the tumor cell lines but they were not cytotoxic against normal cell lines. The crude extract of brown propolis displayed antimicrobial activity against C.â neoformans, methicillin-resistant Staphylococcus aureus, and P.â aeruginosa at 29.9â µg/mL, 178.9â µg/mL, and 160.7â µg/mL, respectively. The volatile fraction inhibited the growth of C.â neoformans at 53.0â µg/mL. The compounds 3-hydroxy-4-methoxybenzaldehyde, 3-methoxy-4-hydroxypropiophenone and 7-oxodehydroabietic acid were active against C.â neoformans, and caffeic and communic acids were active against methicillin-resistant Staphylococcus aureus.
Assuntos
Antibacterianos/farmacologia , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Compostos Fitoquímicos/farmacologia , Própole/química , Animais , Antibacterianos/biossíntese , Antibacterianos/química , Antimaláricos/química , Antimaláricos/metabolismo , Antineoplásicos Fitogênicos/biossíntese , Antineoplásicos Fitogênicos/química , Abelhas , Brasil , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Testes de Sensibilidade Parasitária , Compostos Fitoquímicos/biossíntese , Compostos Fitoquímicos/química , Plasmodium falciparum/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
BACKGROUND: Larrea tridentata is a dominant shrub in the deserts of North America and is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding its chemical composition, the products of the mevalonate, shikimate, and malonate pathways are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant response mediated by nuclear factor erythroid 2-related factor 2 (NRF2). OBJECTIVE AND METHODS: This review seeks to draw attention to metabolites other than NDGA and which also contribute to the various biological activities of L. tridentata. Therefore, the present review includes those reports focused on the pharmacological properties of the organic extracts of L. tridentata and its natural products with promising values. RESULTS AND CONCLUSION: Among the most promising and widely reported metabolites from L. tridentata, are: 3'-demethoxy-6-O-demethylisoguaiacin, 3'-O-methyldihydroguaiaretic acid, meso-dihydroguaiaretic acid, and tetra-O-methylnordihydroguaiaretic acid. These have been reported to exhibit antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.