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1.
J Chem Ecol ; 46(1): 63-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31832894

RESUMO

Plants experience seasonal fluctuations in abiotic and biotic factors such as herbivore attack rates. If and how root defense expression co-varies with seasonal fluctuations in abiotic factors and root herbivore attack rates is not well understood. Here, we evaluated seasonal changes in defensive root latex chemistry of Taraxacum officinale plants in the field and correlated the changes with seasonal fluctuations in abiotic factors and damage potential by Melolontha melolontha, a major natural enemy of T. officinale. We then explored the causality and consequences of these relationships under controlled conditions. The concentration of the defensive sesquiterpene lactone taraxinic acid ß-D glucopyranosyl ester (TA-G) varied substantially over the year and was most strongly correlated to mean monthly temperature. Both temperature and TA-G levels were correlated with annual fluctuations in potential M. melolontha damage. Under controlled conditions, plants grown under high temperature produced more TA-G and were less attractive for M. melolontha. However, temperature-dependent M. melolontha feeding preferences were not significantly altered in TA-G deficient transgenic lines. Our results suggest that fluctuations in temperature leads to variation in the production of a root defensive metabolites that co-varies with expected attack of a major root herbivore. Temperature-dependent herbivore preference, however, is likely to be modulated by other phenotypic alterations.


Assuntos
Besouros/fisiologia , Glucosídeos/metabolismo , Lactonas/metabolismo , Sesquiterpenos/metabolismo , Taraxacum/química , Animais , Biomassa , Besouros/crescimento & desenvolvimento , Glucosídeos/química , Glucosídeos/farmacologia , Herbivoria/efeitos dos fármacos , Lactonas/química , Lactonas/farmacologia , Larva/efeitos dos fármacos , Larva/fisiologia , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Raízes de Plantas/parasitologia , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/parasitologia , Estações do Ano , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Taraxacum/metabolismo , Taraxacum/parasitologia , Temperatura Ambiente
2.
Biosci Biotechnol Biochem ; 84(1): 25-30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31516064

RESUMO

The Japanese orange fly, Bactrocera tsuneonis, infests various citrus crops. While male pheromone components accumulated in the rectal glands are well characterized for Bactrocera, but information regarding the chemical factors involved in the life cycles of B. tsuneonis remains scarce. Herein, several volatile chemicals including a γ-decalactone, (3R,4R)-3-hydroxy-4-decanolide [(3R,4R)-HD], were identified as major components, along with acetamide and spiroketals as minor components in the rectal gland complexes of male B. tsuneonis flies. The lactone (3R,4R)-HD was also identified in female rectal gland complexes. The amount of this compound in mature males was significantly higher than those observed in females and immature males. The lactone (3R,4R)-HD was detected in flies fed with sucrose only, indicating that this lactone is not derived from dietary sources during adulthood, but biosynthesized in vivo. The predominant accumulation of (3R,4R)-HD in mature males also suggests a possible role in reproductive behavior.


Assuntos
Lactonas/química , Glândula de Sal/química , Tephritidae/fisiologia , Acetamidas/síntese química , Acetamidas/química , Animais , Cromatografia Gasosa , Citrus , Dieta , Feminino , Furanos/síntese química , Furanos/química , Japão , Lactonas/síntese química , Masculino , Espectrometria de Massas , Reprodução/fisiologia , Atrativos Sexuais/química , Comportamento Sexual Animal/fisiologia , Compostos de Espiro/síntese química , Compostos de Espiro/química , Sacarose
3.
Chem Commun (Camb) ; 55(94): 14119-14122, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31687686

RESUMO

A new strategy to construct a transient supramolecular peptide amphiphile (SPA) and its vesicular aggregates is displayed. The construction of the amphiphile is assisted by the ternary complexation of cucurbit[8]uril and pH responsive imine bond formation. The transient assembly follows a pH clock set by urea/urease and hydrolysis of glucono delta-lactone (GdL). The transient assembly can be repeated for several cycles through feeding the system with the fuel (urea).


Assuntos
Peptídeos/química , Tensoativos/química , Concentração de Íons de Hidrogênio , Hidrólise , Lactonas/química , Lactonas/metabolismo , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Estrutura Molecular , Peptídeos/síntese química , Tensoativos/síntese química , Ureia/química , Ureia/metabolismo , Urease/química , Urease/metabolismo
4.
J Agric Food Chem ; 67(47): 13040-13050, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31670962

RESUMO

Two new natural 10-membered macrolides (1, 2) and one chromene-4,5-dione derivative (3), named stagonolides J and K and stagochromene A, respectively, were isolated from the phytopathogenic fungus Stagonospora cirsii S-47, together with two known compounds, stagonolide A (4) and herbarumin I (5). Stagonolides J and K and stagochromene A were characterized as (5E,7R*,8S*,9R*)-7,8-dihydroxy-9-propyl-5-nonen-9-olide, (5E,7R,9S)-7-hydroxy-9-propyl-5-nonen-9-olide, and (2R*,3R*)-3-hydroxy-2-propyltetrahydro-2H-chromene-4,5(3H,4aH)-dione, respectively, by spectroscopic (mostly by NMR and ESIMS) data. Compounds 1-5 showed different rates of phytotoxic activity on punctured leaf discs of Sonchus arvensis. The antimicrobial, cytotoxic, and antiprotozoal activity of isolated compounds was also evaluated. Based on our data, stagonolide K and herbarumin I can be proposed as a potential scaffold for the development of a new natural herbicide and estimated as possible selection/quality markers of a bioherbicide based on S. cirsii, while stagonolide A can be considered as a mycotoxin.


Assuntos
Ascomicetos/química , Benzopiranos/química , Herbicidas/química , Compostos Heterocíclicos com 1 Anel/química , Lactonas/química , Macrolídeos/química , Sonchus/efeitos dos fármacos , Benzopiranos/farmacologia , Herbicidas/farmacologia , Compostos Heterocíclicos com 1 Anel/farmacologia , Lactonas/farmacologia , Macrolídeos/farmacologia , Estrutura Molecular , Micotoxinas/química , Micotoxinas/farmacologia , Sonchus/crescimento & desenvolvimento
5.
Eur J Med Chem ; 183: 111726, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585275

RESUMO

Multidrug resistance (MDR) is a main cause of chemotherapy failure and patient death. This situation usually involves a glycoprotein (P-gp) mediated drug efflux, resulting in a low cellular drug concentration and insensitivity. Here we report the design, synthesis and evaluation of novel (+/-)-securinine bivalents as P-gp inhibitors in vitro and in vivo. MTT assays reflected that bivalent mimetics of securinine particularly the virosecurinine bivalent mimetic 8C showed promissing MDR reversal potential in both P-gp highly expressed cell line HepG2/DOX and MCF-7/ADM. At a 10 µM concentration, 8C can entirely reverse the resistance of HepG2/DOX to doxorubicin (DOX), and is more effective than the positive control verapamil (VRP). Fluorescence, flow cytometry, and DOX efflux assays demonstrated that 8C can facilitate the accumulation and diminish the efflux of intracellular DOX. Molecular docking analysis and western blot assays indicated that 8C accomplished this by competitively inhibiting the activity of P-gp rather than by affecting its expression. Compound 8C was also observed to reverse drug resistance effectively in xenograft models when combined with DOX. This study lays a foundation for the discovery of (+/-)-securinine ramifications as P-gp inhibitors and provides a promising lead compound 8C as a P-gp mediated MDR reversal agent.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Alcaloides , Antineoplásicos , Azepinas , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lactonas , Piperidinas , Alcaloides/química , Alcaloides/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Azepinas/química , Azepinas/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Compostos Heterocíclicos de Anel em Ponte/química , Compostos Heterocíclicos de Anel em Ponte/farmacologia , Humanos , Lactonas/química , Lactonas/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Piperidinas/química , Piperidinas/farmacologia , Verapamil/farmacologia
6.
J Food Sci ; 84(10): 2758-2776, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31509249

RESUMO

The changes of volatile compounds in soy sauce during long-term fermentation (12 months) were investigated using solid-phase microextraction (SPME) and stir bar sorptive extraction (SBSE). A total of 144 and 129 compounds were identified in soy sauce with long-term fermentation by SPME and SBSE, respectively. The contents of most compounds, such as acids, aldehydes, benzene and benzene derivatives, esters, lactones, pyrazines, pyrones, and pyrroles, showed a tendency to increase, whereas those of alcohols and ketones decreased according to long-term fermentation. In addition, principal component analysis and partial least squares discriminant analysis were applied to discriminate soy sauce samples according to fermentation periods and determine key volatile compounds related to long-term fermentation. The initial fermentation stages were mainly associated with some alcohols, ketones, and lactones, whereas the later stages were strongly associated with most esters, some phenols, benzene and benzene derivatives, and pyrroles. Moreover, the key volatile compounds associated with long-term fermentation in soy sauce samples were ethyl 3-methylbutanoate (ethyl isovalerate), ethyl pentanoate (ethyl valerate), 1-octen-3-yl acetate, 3-(methylthio)-1-propanol (methionol), ethyl benzoate, ethyl 2-phenylacetate, 1-(1H-pyrrol-2-yl)ethanone (2-acetylpyrrole), and 5-pentyl-2-oxolanone (γ-nonalactone). PRACTICAL APPLICATION: This study investigated changes of volatile compounds in soy sauce during long-term fermentation (12 months) using solid-phase microextraction and stir bar sorptive extraction. In addition, the key volatile compounds associated with long-term fermentation in soy sauce samples were determined. These results may help to predict the effective contributors related to long-term fermentation of soy sauce and improve the quality of soy sauce during long-term fermentation.


Assuntos
Alimentos de Soja/análise , Compostos Orgânicos Voláteis/química , Álcoois/química , Álcoois/isolamento & purificação , Aldeídos/química , Aldeídos/isolamento & purificação , Fermentação , Cetonas/química , Cetonas/isolamento & purificação , Lactonas/química , Lactonas/isolamento & purificação , Microextração em Fase Sólida , Soja/química , Compostos Orgânicos Voláteis/isolamento & purificação
7.
Korean J Parasitol ; 57(4): 359-368, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31533402

RESUMO

In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 µg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.


Assuntos
Antiprotozoários/farmacologia , Compostos de Benzalcônio/farmacologia , Lactonas/farmacologia , Leishmania tropica/efeitos dos fármacos , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/química , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/química , Linhagem Celular , Quimioterapia Combinada , Citometria de Fluxo , Humanos , Lactonas/administração & dosagem , Lactonas/química , Lipossomos
8.
Mater Sci Eng C Mater Biol Appl ; 104: 109952, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499985

RESUMO

The aim of this work is to provide a new kind of polyurethane with improved surface blood compatibility for long-term blood-contacting biomaterials. In the study, an aliphatic poly(ester-urethane) (H-PEU) with uniform-size hard segments was synthesized by one-step chain extension of poly(ε-caprolactone) (PCL) with diurethane diisocyanate (HBH), and biomimetic phosphorylcholine (PC) groups were immobilized onto the film surface with high grafting efficiency by three-step chemical treatments under mild reaction conditions. The H-PEU film was firstly treated with 1,6-hexanediisocyanate (HDI) to introduce -NCO groups on the surface (H-PEU-NCO) through an allophanate reaction; the -NCO groups were then coupled via a condensation reaction with one of -NH2 groups of tris(2-aminoethyl)amine (TAEA) to immobilize -NH2 on the surface (H-PEU-NH2); finally, the double bond of 2-methacryloyloxyethyl phosphorylcholine (MPC) reacted with -NH2 by Michael addition reaction to obtain MPC-grafted H-PEU (H-PEU-MPC). The modified surfaces were characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The results verified that MPC was successfully grafted onto H-PEU surface with high grafting density. The blank and modified films showed similar crystallization behaviors, thermal stabilities and mechanical properties, indicating that the chemical treatments had minimum influence on the physicochemical properties of the substrate. The H-PEU-MPC displaying a much lower water contact angle (~15.2°) than H-PEU (80.3°) meant that the hydrophilic PC functional groups improved the surface hydrophilicity significantly. The surface blood compatibility was examined by bovine serum albumin adsorption and platelet adhesion tests, and the results revealed that H-PEU-MPC had improved resistance to protein adsorption and platelet adhesion capacity. The MPC-grafted H-PEU film possessed outstanding mechanical properties (ultimate stress: 36.1 MPa; strain at break: 883%), low protein adsorption quantity (1.33 µg/cm2) and good anti-platelet adhesion capacity (582 ±â€¯16 per mm2), implying its high potential to be applied as biomaterials for vascular grafts, subcutaneously implanted devices or other blood-contacting devices.


Assuntos
Materiais Biocompatíveis/química , Metacrilatos/química , Fosforilcolina/análogos & derivados , Poliésteres/química , Poliuretanos/química , Adsorção/efeitos dos fármacos , Animais , Caproatos/química , Isocianatos/química , Lactonas/química , Fosforilcolina/química , Adesividade Plaquetária/efeitos dos fármacos , Coelhos , Soroalbumina Bovina/química , Propriedades de Superfície
9.
Planta Med ; 85(14-15): 1136-1142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31539917

RESUMO

Monoamine oxidases (MAOs) are key metabolic enzymes for neurotransmitter and dietary amines and are targets for the treatment of neuropsychiatric and neurodegenerative disorders. This study examined the MAO inhibition potential of kavain and other kavalactones from the roots of kava (Piper methysticum), a plant that has been used for its anxiolytic properties. (±)-Kavain was found to be a good potency in vitro inhibitor of human MAO-B with an IC50 of 5.34 µM. (±)-Kavain is a weaker MAO-A inhibitor with an IC50 of 19.0 µM. Under the same experimental conditions, the reference MAO inhibitor, curcumin, displays IC50 values of 5.01 µM and 2.55 µM for the inhibition of MAO-A and MAO-B, respectively. It was further established that (±)-kavain interacts reversibly and competitively with MAO-A and MAO-B with enzyme-inhibitor dissociation constants (Ki) of 7.72 and 5.10 µM, respectively. Curcumin in turn, displays a Ki value of 3.08 µM for the inhibition of MAO-A. Based on these findings, other kavalactones (dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) were also evaluated as MAO inhibitors in this study. Yangonin proved to be the most potent MAO inhibitor with IC50 values of 1.29 and 0.085 µM for MAO-A and MAO-B, respectively. It may be concluded that some of the central effects (e.g., anxiolytic) of kava may be mediated by MAO inhibition.


Assuntos
Ansiolíticos/farmacologia , Kava/química , Lactonas/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/efeitos dos fármacos , Humanos , Lactonas/química , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Raízes de Plantas/química
10.
Eur J Med Chem ; 182: 111662, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31499358

RESUMO

Classical macrolides containing 14- or 15-membered aglycone lactone rings are basic and widely used antibacterial agents in clinical therapy. Macrolides exert antibacterial effects by blocking the exit peptide tunnel during translation at bacterial ribosomes. However, one macrolide occasionally manifests different docking modes or binding sites at ribosomes, which presents difficulties in designing macrolide modifications. In addition to their medical importance, lactone macrolides possess interesting chemistry driven by numerous intramolecular interactions or cascade transformations. Lactone macrolides are potent antibacterial/bactericidal agents, whereas derivatives of macrolactone antibiotics possess anti-malarial, anti-cancer, anti-inflammatory, and anti-leishmanial activity, and can regulate gastrointestinal motility. Hence, it is important to develop novel semi-synthetic and completely synthetic approaches for functionalising lactone cores of different macrolides and their structural analogues such as ketolides, fluoro-ketolides, acylides, and hybrids containing steroids, nucleosides, heterocycles, and peptides. Here, we discuss modifications that generate novel macrolides with enhanced biological potency and improved molecular mechanisms of action. The bibliography presented in this review contains references to articles and patents that were published and filed from 2009 to mid-2019.


Assuntos
Antibacterianos/farmacologia , Lactonas/farmacologia , Macrolídeos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Humanos , Lactonas/síntese química , Lactonas/química , Macrolídeos/química , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
11.
Mater Sci Eng C Mater Biol Appl ; 104: 110006, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499941

RESUMO

The present work shows the development and evaluation of the veterinary antibiotic cloxacillin benzathine (CLOXB) loaded into poly-ε-caprolactone (PCL) nanocapsules (NC), as a potential new treatment strategy to manage bovine intramammary infections, such as mastitis. Staphylococcus aureus-induced mastitis is often a recurrent disease due to the persistence of bacteria within infected cells. CLOXB-PCL NC were prepared by interfacial deposition of preformed biodegradable polymer followed by solvent displacement method. The mean diameter of NC varied from 241 to 428 nm and from 326 to 375 nm, when determined by dynamic light scattering and by atomic force microscopy, respectively. The zeta potential of NC was negative and varied from -28 to -51 mV. In vitro release studies from the NC were performed in two media under sink conditions: PBS with 1% polyethylene glycol or milk. A reversed-phase HPLC method was developed to determine the NC entrapment efficiency and kinetics of CLOXB release from the NC. Free CLOXB dissolution occurred very fast in both media, while drug release from the NC was slower and incomplete (below 50%) after 9 h. CLOXB release kinetics from polymeric NC was fitted with the Korsmeyer-Peppas model indicating that CLOXB release is governed by diffusion following Fick's law. The fluorescence confocal microscopy images of macrophage-like J774A.1 cells reveal NC uptake and internalization in vitro. In addition, antimicrobial effect of the intramammary administration of CLOXB-PCL NC in cows with mastitis resulted in no clinical signs of toxicity and allowed complete pathogen elimination after treatment. The in vivo results obtained in this work suggest that CLOXB-PCL NC could be a promising formulation for the treatment of intramammary infections in cattle, considering their physicochemical properties, release profiles and effects on bovine mastitis control.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Cloxacilina/análogos & derivados , Cloxacilina/química , Etilenodiaminas/química , Nanocápsulas/química , Polímeros/química , Animais , Caproatos/química , Bovinos , Linhagem Celular , Difusão , Feminino , Lactonas/química , Mastite Bovina , Camundongos , Leite/microbiologia , Polietilenoglicóis/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos
12.
J Agric Food Chem ; 67(38): 10764-10773, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31487158

RESUMO

It has been hypothesized that the α-methylene-γ-lactone moiety of sesquiterpene lactones is a key unit for their bioactivity. As a consequence, modifications of these compounds have been focused on this fragment. In the work reported here, two sesquiterpene lactones, namely, dehydrocostuslactone and ß-cyclocostunolide, a eudesmanolide obtained by controlled cyclization of costunolide, were chosen for modification by Michael addition at C-13. On applying this reaction to both compounds, it was possible to introduce the functional groups alkoxy, amino, carbamoyl, hydroxy, and thiol to give products in good to high yields, depending on the base and solvent employed. In particular, the introduction of a thiol group at C-13 in both compounds was achieved with outstanding yields (>90%) and this is unprecedented for these sesquiterpene lactones. The bioactivities of the products were evaluated on etiolated wheat coleoptile elongation and germination of seeds of parasitic weeds, with significant activity observed on Orobanche cumana and Phelipanche ramosa. The structure-activity relationships are discussed.


Assuntos
Lactonas/química , Orobanchaceae/química , Orobanche/química , Extratos Vegetais/química , Plantas Daninhas/química , Sesquiterpenos/química , Germinação , Estrutura Molecular , Orobanchaceae/crescimento & desenvolvimento , Orobanche/crescimento & desenvolvimento , Plantas Daninhas/crescimento & desenvolvimento , Sementes/química , Sementes/crescimento & desenvolvimento , Compostos de Sulfidrila/química
13.
Comput Biol Chem ; 83: 107112, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31480006

RESUMO

Prostate cancer is a common cause of death in men and a novel treating methods should be developed. In order to find a new drug for prostate cancer, a series of novel conformationally constrained analogues of (+)-goniofufurone and 7-epi-(+)-goniofufurone, as well as the newly synthesized styryl lactones containing the cinnamic acid ester groups were evaluated for in vitro cytotoxicity against prostate cancer cell (PC-3). Furthermore, prediction of physicochemical characteristics and drugability as well as in silico ADME-Tox tests of investigated compounds were performed. The 3D-QSAR model was established using the comparative molecular field analysis method. According to obtained results, the tricyclic compounds 9 and 10 had the highest potency with IC50 < 20 µM. Evaluation of structural features through 3D-QSAR model identified steric field feature on the cinnamic acid ester groups at C-7 as a crucial for the cytotoxic activity. This research suggests that most of the analysed compounds have desirable properties for drug candidates and high potential in drug development, which recommend them for further research in treatment of prostate cancer. Furthermore, obtained 3D-QSAR model is able to successfully identify styryl lactones that have significant cytotoxic activity and provide information for screening and design of novel inhibitors against PC-3 cell line that could be used as drugs in treatment of the prostate cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Lactonas/farmacologia , Relação Quantitativa Estrutura-Atividade , Estirenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/metabolismo , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/metabolismo , Modelos Moleculares , Células PC-3 , Estirenos/química , Estirenos/metabolismo
14.
Molecules ; 24(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480332

RESUMO

Multistep chromatographic separations of the chloroform extract of the Turkish endemic plant Psephellus pyrrhoblepharus (Boiss.) Wagenitz (syn. Centaurea pyrrhoblephara Boiss.) resulted in the isolation of six guaianolid-type sesquiterpenes, chlorojanerin (1), 19-deoxychlorojanerin (2), 15-hydroxyjanerin (3), aguerin B (4), cynaropicrin (5), eleganin (6); three flavonoids, apigenin, 6-methoxyluteolin and jaceosidine; two glycosides, benzyl-1-O-ß-d-glucoside and 3(Z)-hexenyl-1-O-ß-d-glucoside; and the coumarin scopoletin. The structures were established by the interpretation of their ESI-MS and 1D and 2D NMR data including 1H-NMR, JMOD, 1H,1H-COSY, HSQC, HMBC, and NOESY experiments. All compounds were isolated for the first time from P. pyrrhoblepharus. Compounds 1-6, the isolated flavonoids and scopoletin were evaluated for their antiproliferative activities on human gynecological cancer cell lines (SiHa, HeLa, and MDA-MB-231 cells) using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Chlorojanerin (1), 19-deoxychlorojanerin (2), aguerin B (4), cynaropicrin (5), eleganin (6) were shown to have noteworthy effects on all of the tested cell lines, while apigenin, jaceosidine, and 6-methoxyluteolin were moderately active on HeLa cells. The highest activities were demonstrated by the chlorine-containing derivatives chlorojanerin (1) and 19-deoxychlorojanerin (2) with IC50 values of 2.21 and 2.88 µM, respectively, against the triple negative breast cancer model MDA-MB-231 cells.


Assuntos
Asteraceae/química , Flavonoides/farmacologia , Neoplasias dos Genitais Femininos/patologia , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Lactonas/química , Espectroscopia de Prótons por Ressonância Magnética , Sesquiterpenos/química
15.
Molecules ; 24(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484419

RESUMO

Chemical investigation of Cordia millenii, Baker resulted in the isolation of a new depsidone, cordidepsine (1), along with twelve known compounds including cyclooctasulfur (2), lup-20(29)-en-3-triacontanoate (3), 1-(26-hydroxyhexacosanoyl)glycerol (4), glyceryl-1-hexacosanoate (5) betulinic acid (6), lupenone (7), ß-amyrone (8), lupeol (9), ß-amyrin (10), allantoin (11), 2'-(4-hydroxyphenyl)ethylpropanoate (12) and stigmasterol glycoside (13). Hemi-synthetic reactions were carried out on two isolated compounds (5 and 6) to afford two new derivatives, that is, cordicerol A (14) and cordicerol B (15), respectively. The chemical structures of all the compounds were established based on analysis and interpretation of spectroscopic data such as electron ionization mass spectrometry (EI-MS), high resolution electrospray ionization mass spectrometry (HR-ESI-MS), fast atom bombardment mass spectrometry (FAB-MS), one dimension and two dimension nuclear magnetic resonance (1D and 2D-NMR) spectral data as well as X-ray crystallography (XRC). Lupeol ester derivatives [Lup-20(29)-en-3-triacontanoate (3)], monoglycerol derivatives [1-(26-hydroxyhexacosanoyl)glycerol (4) and glyceryl-1 hexacosanoate (5)] were isolated for the first time from Cordia genus while sulfur allotrope [cyclooctasulfur (2)] was isolated for the first time from plant origin. Biological assays cordidepsine (1) exhibited significant anti-HIV integrase activity with IC50 = 4.65 µM; EtOAc extract of stem barks, EtOAc fraction of roots and leaves were not toxic against 3T3 cells.


Assuntos
Fármacos Anti-HIV/química , Cordia/química , Depsídeos/química , Lactonas/química , Extratos Vegetais/química , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Espectrometria de Massas
16.
J Chem Ecol ; 45(9): 768-778, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31493166

RESUMO

Ithomiine butterflies use pyrrolizidine alkaloids (PAs) as precursors for male pheromones, such as dihydropyrrolizines or lactones. In contrast to most other ithomiine genera, none of these compounds have ever been detected in Oleria species. The absence of these compounds is thought to be the result of limited access to PA-containing plants. Here we investigate the contents of the androconia of Oleria onega caught in the wild when PA containing plants were abundant. Although the PA lycopsamine was detected in the hairpencils, none of the other known PA-derived compounds were present. Instead, the unsubstituted core of the PA necine base, 1-methylene-1H-pyrrolizine (13), a very unstable compound, was found. The identity of this compound was proven by synthesis. Although its formation in nature appears very likely, 13 is also formed during GC analysis of PAs, making its natural occurrence uncertain. Nevertheless, its reactivity makes it a good candidate for a signaling compound, because its rapid degradation can be used to convey spatial and temporal information. In addition, several other compounds, likely used in intraspecific communication, were identified. All of these compounds are reported for the first time as natural products or from insects. These include 9-hydroxynonanoic acid (21) and (Z)-9-hydroxy-6-enoic acid (18), as well as their condensation products with 11-hexadecenoic- and octadecenoic acids. Furthermore, self-condensation products, such as (Z)-9-[(9-hydroxynon-6-enoyl)oxy]- and 9-[(9-hydroxynonanoyl)oxy]nonanoic acid and non-6-enoic acids (35, 36, 38, 40) were identified, together with the known compounds 2-heptadecanol (39) and 6,10,14-trimethylpentadecan-2-ol (37). In summary, O. onega appears to lack enzymes to produce dihydropyrrolizines. In stark contrast to other ithomiine genera, a unique blend of oxidized fatty acids seems to be used instead.


Assuntos
Borboletas/metabolismo , Feromônios/química , Alcaloides de Pirrolizidina/química , Animais , Produtos Biológicos/química , Borboletas/química , Cromatografia Gasosa , Ácidos Graxos/química , Lactonas/química , Masculino
17.
J Appl Microbiol ; 127(5): 1468-1478, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31403229

RESUMO

AIMS: Medicinal plant-associated endophytic fungi are important sources of precious bioactive compounds, contributing more than 80% of the natural drugs for various ailments. The present study was aimed at evaluating the anticancer activity of the crystallized compound alternariol methyl ether (AME) against hepatocellular carcinoma (HCC) both in vitro and in vivo from an endophytic fungus residing in the medicinal plant Vitex negundo. METHODS AND RESULTS: The secondary metabolites from the endophytic fungus Alternaria alternata MGTMMP031 were isolated. Purification and characterization of the compound was performed and the potential compound was identified as AME. The crystal structure of AME was unambiguously confirmed by X-ray analysis. AME has been checked for its antibacterial and anticancer properties which showed its effectiveness against various bacteria and demonstrated marked anti-proliferative activity against the human HCC cells (HUH-7) both in vitro and in vivo. Mode of actions included cell cycle arrest, reducing the level of markers enzymes of liver cancer and preventing tumour growth. CONCLUSIONS: Alternariol methyl ether acts as a potential therapeutic target against HCC. The compound was isolated and the crystal structure was obtained for the first time from the endophytic fungus A. alternata MGTMMP031. In the present study, the crystallized structure of AME was obtained by slow evaporation technique. It can be concluded that AME acts as a potential therapeutic target against HCC. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi residing in the medicinal plants have strong biological significance and bioactive compounds from these fungi provide better therapeutic targets against diseases.


Assuntos
Alternaria/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Endófitos/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Éteres Metílicos/química , Plantas Medicinais/microbiologia , Alternaria/isolamento & purificação , Alternaria/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/fisiopatologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cristalização , Endófitos/isolamento & purificação , Endófitos/metabolismo , Humanos , Lactonas/química , Lactonas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/fisiopatologia , Éteres Metílicos/isolamento & purificação , Éteres Metílicos/farmacologia , Metabolismo Secundário
18.
Carbohydr Res ; 483: 107754, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398613

RESUMO

Dermatan sulfate oligosaccharides having reducing end 2,5-anhydro-d-talose were prepared by partial N-deacetylation of dermatan sulfate polysaccharide with hydrazine followed by deamination with nitrous acid, and the effect of these oligosaccharides on the activity of bovine testicular hyaluronidase was investigated. Hydrolysis activity and transglycosylation activity of this enzyme were assessed in an independent reaction system by analyzing the products by HPLC. Dermatan sulfate oligosaccharides inhibited hyaluronan hydrolysis by bovine testicular hyaluronidase. Kinetic analysis of the hydrolysis reaction revealed that the inhibition mode by dermatan sulfate oligosaccharides was as competitive as that previously shown by chondroitin sulfate oligosaccharides. Transglycosylation of hyaluronan by bovine testicular hyaluronidase, as a reverse reaction of hydrolysis of hyaluronan, was also inhibited. These inhibitory effects were dependent on the dose and sulfation degree of dermatan sulfate.


Assuntos
Inibidores Enzimáticos/síntese química , Hialuronoglucosaminidase/antagonistas & inibidores , Oligossacarídeos/síntese química , Testículo/enzimologia , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Dermatan Sulfato/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Ácido Hialurônico/química , Lactonas/química , Masculino , Oligossacarídeos/química , Oligossacarídeos/farmacologia
19.
Fitoterapia ; 138: 104312, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31419464

RESUMO

The Alpine wormwood Artemisia vallesiaca All. was considered the most valuable ingredient of vermouth, a celebrated aromatized wine. A. vallesiaca has a very limited geographical distribution, and the booming market of vermouth decimated its natural population, resulting in the eventual replacement of this rare species with more common and less expensive wormwoods like A. absinthium L.. Over the past years, attempts to revive the original recipe(s) of vermouth have fostered the establishment of cultivations of A. vallesiaca in pre-montane settings. In order to assist these projects, the phytochemical profile of cultivated plants and of several native populations of A. vallesiaca from the Swiss Valais were comparatively evaluated, focusing on sesquiterpene lactones and on lipophilic flavonoids, the hallmark constituents of Artemisia species. Remarkably, no significant difference was detected between the samples, despite the different origins. The lipophilic flavonoids of A. vallesiaca were similar to those of related species used in the production of vermouth, but the presence of C-9 oxygenated 11ß-methyl germacranolides and eudesmanolides (herbolides) made its sesquiterpene lactone profile peculiar. In addition to known compounds, two novel germacranolides were also characterized (herbolides J and K), and the major sesquiterpene lactone from the plant, the bitter germacranolide herbolide D (4), was detected and quantified by 1H NMR in a bitter liqueur aromatized with A. vallesiaca. Taken together, these observations qualify herbolides as marker to identify A. vallesiaca in aromatized alcohol matrixes.


Assuntos
Artemisia/química , Lactonas/química , Sesquiterpenos de Germacrano/química , Vinho , Itália , Compostos Fitoquímicos/química
20.
Chem Commun (Camb) ; 55(74): 11017-11020, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31424070

RESUMO

Synthesis of adipic acid, a key monomer of nylon-66 and polyurethane, from biomass is highly attractive for establishing green and sustainable chemical processes. Here, we report that zirconia-supported rhenium oxide (ReOx/ZrO2) efficiently catalyses the deoxydehydration of cellulose-derived d-glucaric acid, offering adipic acid ester with a yield of 82% by combining with a Pd/C catalyst in subsequent reactions.


Assuntos
Adipatos/síntese química , Ésteres/síntese química , Rênio/química , Zircônio/química , Biomassa , Carbono/química , Catálise , Ácido Glucárico/química , Lactonas/química , Oxirredução , Paládio/química , Estereoisomerismo
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