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1.
Molecules ; 26(21)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34770993

RESUMO

Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 µg·mL-1. In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2). Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ginkgo biloba/química , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Salicilatos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Salicilatos/química , Salicilatos/isolamento & purificação , Células Tumorais Cultivadas
2.
Int J Mol Sci ; 22(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34681798

RESUMO

Salix cortex-containing medicine is used against pain conditions, fever, headaches, and inflammation, which are partly mediated via arachidonic acid-derived prostaglandins (PGs). We used an activity-guided fractionation strategy, followed by structure elucidation experiments using LC-MS/MS, CD-spectroscopy, and 1D/2D NMR techniques, to identify the compounds relevant for the inhibition of PGE2 release from activated human peripheral blood mononuclear cells. Subsequent compound purification by means of preparative and semipreparative HPLC revealed 2'-O-acetylsalicortin (1), 3'-O-acetylsalicortin (2), 2'-O-acetylsalicin (3), 2',6'-O-diacetylsalicortin (4), lasiandrin (5), tremulacin (6), and cinnamrutinose A (7). In contrast to 3 and 7, compounds 1, 2, 4, 5, and 6 showed inhibitory activity against PGE2 release with different potencies. Polyphenols were not relevant for the bioactivity of the Salix extract but salicylates, which degrade to, e.g., catechol, salicylic acid, salicin, and/or 1-hydroxy-6-oxo-2-cycohexenecarboxylate. Inflammation presents an important therapeutic target for pharmacological interventions; thus, the identification of relevant key drugs in Salix could provide new prospects for the improvement and standardization of existing clinical medicine.


Assuntos
Inflamação/tratamento farmacológico , Salicilatos/isolamento & purificação , Salix/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Células Cultivadas , Cromatografia Líquida , Dinoprostona/metabolismo , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Dor/tratamento farmacológico , Fitoterapia/métodos , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Salicilatos/análise , Salicilatos/farmacologia , Espectrometria de Massas em Tandem
3.
Curr Pharm Biotechnol ; 21(13): 1289-1297, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250223

RESUMO

Parmelia that belongs to the Parmeliaceae Family is a foliose lichen combined with one or two groups of fungi in Phylum Ascomycota or Basidiomycota and algae, which might be green algae or blue-green algae (cyanobacteria). It is generally called "Stone Flower," "Charila," "Pattharphool," or "Shilaaapushpa" in India. Lichen can be generally found growing on walls, old trees and spread largely across India, especially in the mountain area. It is a source of edible organisms for people residing in some regions of Nepal and it is also cultivated in hillsides of Kashmir. It has been found that lichen contains a lot of distinctive chemical compounds such as evernic acid, lecanoric acid, lobaric acid, norstictic acid, physodic acid, and salazinic acid. Some species of this lichen are recommended traditionally for controlling diseases such as boils, bronchitis, inflammations, excessive salivation, toothache, vomiting, etc. It has also applied as an indicator for biomonitoring, astringent, carminative, demulcent, bitter, resolvent, emollient, laxative, sporofic, sedative, diuretic and considered for treating sores, bronchitis, excessive salivation, vomiting, tooth-ache, boils and inflammations. It has been utilized for preparing traditional food and acts as a bioindicator for air pollution and radiation. It shows antibacterial, antioxidant, antimycobacterial and antifungal activities, including haemolytic, anaesthetic, spasmolytic and antispasmodic and antitumour activities. It also has several unique phytoconstituents that could be in charge of different therapeutic activities, but the majority of them are still unexplored. The review mainly focuses on various facets, such as common names, synonyms, traditional uses, botanical descriptions, and pharmacological activities of seven species of Parmelia.


Assuntos
Hidroxibenzoatos/farmacologia , Lactonas/farmacologia , Parmeliaceae/crescimento & desenvolvimento , Salicilatos/farmacologia , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Humanos , Hidroxibenzoatos/isolamento & purificação , Lactonas/isolamento & purificação , Medicina Tradicional , Parmeliaceae/química , Parmeliaceae/classificação , Salicilatos/isolamento & purificação
4.
J Sep Sci ; 42(6): 1202-1209, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30653252

RESUMO

A valid and reliable method was established to separate six compounds from pigeon pea leaves via elution-extrusion counter-current chromatography. A solvent system composed of n-hexane/methanol/formic acid aqueous solution with pH = 3 (10:6:4, v/v) was screened to achieve satisfactory isolation from the ethanol extract of pigeon pea leaves. Four compounds, 9.2 mg of compound 1 (96.8%), 3.2 mg of 2 (88.0%), 6.2 mg of 4 (94.2%) and 25.2 mg of 5 (94.2%), were obtained by conventional elution from 100 mg of the precipitation fraction, respectively. Two compounds, 14.4 mg of 3 (96.3%) and 28.1 mg of 6 (96.6%), with high K values were obtained by the subsequent extrusion procedure. The compounds 1-6 were identified as 3-methoxy-5-(2-phenylethenyl)-phenol, pinostrobin chalcone, pinostrobin, 2-hydroxy-4-methoxy-6-(2-phenylvinyl)-benzoic acid, longistylin C and cajaninstilbene acid by quadrupole time-of-flight mass spectrometry, and 1 H and 13 C NMR spectroscopy. The in vitro antiproliferation activities of compounds 1, 5 and 6 against human hepatoma cell were evaluated and the half-maximum inhibitory concentrations were acquired.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ácido Benzoico/farmacologia , Flavanonas/farmacologia , Fenóis/farmacologia , Pisum sativum/química , Salicilatos/farmacologia , Estilbenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ácido Benzoico/química , Ácido Benzoico/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Distribuição Contracorrente , Ensaios de Seleção de Medicamentos Antitumorais , Flavanonas/química , Flavanonas/isolamento & purificação , Células Hep G2 , Humanos , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Folhas de Planta/química , Salicilatos/química , Salicilatos/isolamento & purificação , Estilbenos/química , Estilbenos/isolamento & purificação
5.
Bioorg Med Chem ; 26(22): 5845-5851, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420328

RESUMO

Herein we report the anti-inflammatory activity of lobaric acid and pseudodepsidones isolated from the nordic lichen Stereocaulon paschale. Lobaric acid (1) and three compounds (2, 7 and 9) were found to inhibit the NF-κB activation and the secretion of pro-inflammatory cytokines (IL-1ß and TNF-α) in LPS-stimulated macrophages. Inhibition and docking simulation experiments provided evidence that lobaric acid and pseudodepsidones bind to PPAR-γ between helix H3 and the beta sheet, similarly to partial PPAR-γ agonists. These findings suggest that lobaric acid and pseudodepsidones reduce the expression of pro-inflammatory cytokines by blocking the NF-κB pathway via the activation of PPAR-γ.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Depsídeos/farmacologia , Lactonas/farmacologia , Líquens/química , NF-kappa B/antagonistas & inibidores , PPAR gama/agonistas , Salicilatos/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Depsídeos/química , Depsídeos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , NF-kappa B/metabolismo , PPAR gama/metabolismo , Salicilatos/química , Salicilatos/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Células U937
6.
J Sep Sci ; 41(23): 4379-4386, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30302914

RESUMO

An efficient coordination high-speed counter-current chromatography method for the preparative separation of ginkgolic acids from the sarcotesta of Ginkgo biloba L was developed. The type, concentration, and mechanism of the coordination agent were investigated. Following the use of four types of metal salts including silver nitrate, copper chloride, ferric chloride, and aluminium nitrate, n-heptane/ethyl acetate/methanol/acetic acid 5:4:1:1, v/v with 0.20 mol/L silver nitrate as the coordination agent was chosen as the optimum two-phase solvent system. Five main ginkgolic acids including C13:0, C15:0, C15:1, C17:1, and C17:2 were successfully separated with purities greater than 98%. The sample loading was 500 mg, the flow-rate was 2.0 mL/min, rotation speed was 800 rpm and temperature was 20°C. The structures of the separated ginkgolic acids were identified by comparison with standard samples and electrospray ionization mass spectrometry. The introduction of coordination chemistry in high-speed counter-current chromatography is novel and effective for the preparative separation and isolation of ginkgolic acids from the sarcotesta of Ginkgo biloba L and could also be applied to separate compounds which form coordination bonds in other complex natural products.


Assuntos
Ginkgo biloba/química , Extratos Vegetais/isolamento & purificação , Salicilatos/isolamento & purificação , Distribuição Contracorrente , Estrutura Molecular , Extratos Vegetais/química , Salicilatos/química
7.
Molecules ; 23(3)2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29538328

RESUMO

Lobaric acid and lobarstin, secondary metabolites derived from the antarctic lichen Stereocaulon alpnum, exert various biological activities, including antitumor, anti-proliferation, anti-inflammation, and antioxidant activities. However, the underlying mechanisms of these effects have not yet been elucidated in human cervix adenocarcinoma and human colon carcinoma. In the present study, we evaluated the anticancer effects of lobaric acid and lobarstin on human cervix adenocarcinoma HeLa cells and colon carcinoma HCT116 cells. We show that the proliferation of Hela and HCT116 cells treated with lobaric acid and lobarstin significantly decreased in a dose- and time-dependent manner. Using flow cytometry analysis, we observed that the treatment with these compounds resulted in significant apoptosis in both cell lines, following cell cycle perturbation and arrest in G2/M phase. Furthermore, using immunoblot analysis, we investigated the expression of cell cycle and apoptosis-related marker genes and found a significant downregulation of the apoptosis regulator B-cell lymphoma 2 (Bcl-2) and upregulation of the cleaved form of the poly (ADP-ribose) polymerase (PARP), a DNA repair and apoptosis regulator. These results suggest that lobaric acid and lobarstin could significantly inhibit cell proliferation through cell cycle arrest and induction of apoptosis via the mitochondrial apoptotic pathway in cervix adenocarcinoma and colon carcinoma cells. Taken together, our data suggests that lobaric acid and lobarstin might be novel agents for clinical treatment of cervix adenocarcinoma and colon carcinoma.


Assuntos
Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Neoplasias do Colo/metabolismo , Hidroxibenzoatos/farmacologia , Lactonas/farmacologia , Líquens/química , Salicilatos/farmacologia , Neoplasias do Colo do Útero/metabolismo , Antineoplásicos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Depsídeos/química , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Células HeLa , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/isolamento & purificação , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Salicilatos/química , Salicilatos/isolamento & purificação , Neoplasias do Colo do Útero/tratamento farmacológico
8.
Talanta ; 181: 197-203, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29426501

RESUMO

A method to introduce target analytes to a chromatograph from a single drop of whole blood was investigated for minimally invasive monitoring of anionic pharmaceuticals. In this work, salicylate and loxoprofen were examined as organic anions. A micro ion extractor (MIE) has been developed for extraction of inorganic trace anions from whole blood, but this device is not suitable for extraction of pharmaceuticals. In the present study, we improved and optimized the MIE device for organic anion extraction. Various supported liquid membranes were evaluated for use as the ion transfer membrane, with each membrane placed between a droplet sample (donor) and an acceptor solution. A supported liquid membrane of porous polypropylene impregnated with 1-butanol was selected. In addition, the methods for electric field creation and electrode contact were examined to improve the characteristics of the MIE device. The current and extraction time were also optimized. With the optimized method, salicylate and loxoprofen were successfully extracted from a single drop of whole blood. Changes in the concentrations of these pharmaceuticals in blood over time were monitored after administration. As only 25µL of whole blood was required for analysis, repeat measurements could be conducted to monitor changes in the concentrations. This MIE will be useful for monitoring pharmaceutical concentrations in blood.


Assuntos
Análise Química do Sangue/métodos , Coleta de Amostras Sanguíneas/métodos , Membranas Artificiais , Preparações Farmacêuticas/isolamento & purificação , Animais , Ânions/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Cavalos , Humanos , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/química , Fenilpropionatos/sangue , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Diálise Renal/instrumentação , Diálise Renal/métodos , Reprodutibilidade dos Testes , Salicilatos/sangue , Salicilatos/química , Salicilatos/isolamento & purificação , Fatores de Tempo
9.
Fitoterapia ; 120: 164-170, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28625729

RESUMO

Ten new salicyloid derivatives, namely vaccinols J-S (1-10), along with five known compounds (11-15) were isolated from Pestalotiopsis vaccinii (cgmcc3.9199) endogenous with the mangrove plant Kandelia candel (L.) Druce (Rhizophoraceae). Their structures including absolute configurations were established on the basis of spectroscopic analysis, optical rotation, CD spectra, quantum ECD calculations. To the best of our knowledge, vaccinol J (1) is the first example of salicyloid derivatives containing 2-methylfuran moiety. All of the new compounds were tested for their anti-enterovirus 7l (EV71) and cytotoxic activities. Among them, vaccinol J (1) exhibited in vitro anti-EV71 with IC50 value of 30.7µM (IC50 177.0µM for the positive control ribavirin).


Assuntos
Rhizophoraceae/microbiologia , Salicilatos/farmacologia , Xylariales/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Linhagem Celular Tumoral , Enterovirus Humano A/efeitos dos fármacos , Humanos , Estrutura Molecular , Salicilatos/isolamento & purificação
10.
Phytochemistry ; 137: 156-164, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28222890

RESUMO

Chemical investigation of the methanol extract of the fertile form of Roccella montagnei collected in Vietnam afforded twelve secondary metabolites, including five new montagnetol derivatives, orsellinylmontagnetols A-D and a furanyl derivative together with seven known compounds. Their chemical structures were elucidated by analysis of 1D and 2D NMR and high resolution mass spectroscopic data. The relative stereochemistry of two chiral centers (C-2 and C-3) of orsellinylmontagnetols A and B was elucidated by comparison of their coupling constants and the specific rotation with those reported in the literature while the absolute stereochemistry was determined by the application of a modified Mosher method for the hydroxy group at C-3. The absolute configuration (2R,3S) of the butanetetraol moiety of these compounds is in accordance with that of erythrin, a recognized chemotaxonomic marker of the genus Roccella. Five of these compounds were evaluated for their cytotoxic activities against four cancer cell lines. Only orsellinylmontagnetol A exerted a moderate activity against MCF-7 cell line with an IC50 value of 68.39 ± 3.46 µM.


Assuntos
Antineoplásicos/química , Ascomicetos/química , Eritritol/química , Líquens/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Eritritol/análogos & derivados , Eritritol/isolamento & purificação , Humanos , Estrutura Molecular , Salicilatos/química , Salicilatos/isolamento & purificação , Vietnã
11.
J Nat Prod ; 79(1): 2-12, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26731300

RESUMO

A known (1) and a structurally related new natural product (2), both belonging to the amorfrutin benzoic acid class, were isolated from the roots of Glycyrrhiza foetida. Compound 1 (amorfrutin B) is an efficient agonist of the nuclear peroxisome proliferator activated receptor (PPAR) gamma and of other PPAR subtypes. Compound 2 (amorfrutin C) showed comparably lower PPAR activation potential. Amorfrutin C exhibited striking antiproliferative effects for human colorectal cancer cells (HT-29 and T84), prostate cancer (PC-3), and breast cancer (MCF7) cells (IC50 values ranging from 8 to 16 µM in these cancer cell lines). Notably, amorfrutin C (2) showed less potent antiproliferative effects in primary colon cells. For HT-29 cells, compound 2 induced G0/G1 cell cycle arrest and modulated protein expression of key cell cycle modulators. Amorfrutin C further induced apoptotic events in HT-29 cells, including caspase activation, DNA fragmentation, PARP cleavage, phosphatidylserine externalization, and formation of reactive oxygen species. Mechanistic studies revealed that 2 disrupts the mitochondrial integrity by depolarization of the mitochondrial membrane (IC50 0.6 µM) and permanent opening of the mitochondrial permeability transition pore, leading to increased mitochondrial oxygen consumption and extracellular acidification. Structure-activity-relationship experiments revealed the carboxylic acid and the hydroxy group residues of 2 as fundamental structural requirements for inducing these apoptotic effects. Synergy analyses demonstrated stimulation of the death receptor signaling pathway. Taken together, amorfrutin C (2) represents a promising lead for the development of anticancer drugs.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Glycyrrhiza/química , Mitocôndrias/metabolismo , Salicilatos/isolamento & purificação , Salicilatos/farmacologia , Antineoplásicos Fitogênicos/química , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células HT29 , Humanos , Concentração Inibidora 50 , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estrutura Molecular , Marrocos , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Raízes de Plantas/química , Espécies Reativas de Oxigênio/metabolismo , Salicilatos/química , Relação Estrutura-Atividade , Proteína X Associada a bcl-2/metabolismo
12.
Pharm Biol ; 54(9): 1748-62, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26704132

RESUMO

Context Since methods utilised in the treatment of glioblastoma multiforme (GBM) are inadequate and have too many side effects, usage of herbal products in the treatment process comes into prominence. Lichens are symbiotic organisms used for medicinal purposes for many years. There are various anticancer treatments about components of two lichen species used in the present study. Objective Antitumor potential of three lichen secondary metabolites including olivetoric acid (OLA) and physodic acid (PHA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) and psoromic acid (PSA) isolated from Rhizoplaca melanophthalma (DC.) Leuckert (Lecanoraceae) were investigated on human U87MG-GBM cell lines and primary rat cerebral cortex (PRCC) cells for the first time. Materials and methods PRCC cells used as healthy brain cells were obtained from Sprague-Dawley rats. The treatments were carried out on the cells cultured for 48 h. Cytotoxic effects of different concentrations (2.5, 5, 10, 20 and 40 mg/L) of metabolites on the cells were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. Total antioxidant capacity (TAC) and total oxidant status (TOS) parameters were used for assessing oxidative alterations. Oxidative DNA damage potentials of metabolites were investigated via evaluating 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels. Results Median inhibitory concentration (IC50) values of OLA, PHA and PSA were 125.71, 698.19 and 79.40 mg/L for PRCC cells and 17.55, 410.72 and 56.22 mg/L for U87MG cells, respectively. It was revealed that cytotoxic effects of these metabolites showed positive correlation with concentration, LDH activity and oxidative DNA damage. Discussion and conclusion The present findings obtained in this study revealed that primarily OLA and then PSA had high potential for use in the treatment of GBM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzoxepinas/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Ácidos Carboxílicos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Dibenzoxepinas/farmacologia , Glioblastoma/tratamento farmacológico , Líquens , Neurônios/efeitos dos fármacos , Extratos Vegetais/farmacologia , Salicilatos/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Benzoxepinas/isolamento & purificação , Benzoxepinas/toxicidade , Biomarcadores/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Ácidos Carboxílicos/isolamento & purificação , Ácidos Carboxílicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Córtex Cerebral/metabolismo , Dano ao DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Dibenzoxepinas/isolamento & purificação , Dibenzoxepinas/toxicidade , Relação Dose-Resposta a Droga , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , L-Lactato Desidrogenase/metabolismo , Líquens/química , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Ratos Sprague-Dawley , Salicilatos/isolamento & purificação , Salicilatos/toxicidade , Fatores de Tempo
13.
J Nat Prod ; 78(5): 1160-4, 2015 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-25938459

RESUMO

Amorfrutins are isoprenoid-substituted benzoic acid derivatives, which were found in Amorpha fruticosa L. (bastard indigo) and in Glycyrrhiza foetida Desf. (licorice). Recently, amorfrutins were shown to be selective activators of the nuclear receptor PPARγ. Here, we investigated the effects and PPARγ-based mechanisms of reducing inflammation in colon cells by treatment with amorfrutins. In TNF-α-stimulated colon cells amorfrutin A (1) reduced significantly the expression and secretion of several inflammation mediators, in part due to interaction with PPARγ. These results support the hypothesis that amorfrutins may have the potential to treat inflammation disorders such as chronic inflammatory bowel diseases.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Fabaceae/química , PPAR gama/agonistas , Salicilatos/isolamento & purificação , Salicilatos/farmacologia , Estilbenos/isolamento & purificação , Estilbenos/farmacologia , Anti-Inflamatórios/química , Glycyrrhiza/metabolismo , Estrutura Molecular , Receptores Citoplasmáticos e Nucleares/metabolismo , Salicilatos/química , Estilbenos/química , Fator de Necrose Tumoral alfa/farmacologia
14.
Chem Biodivers ; 12(3): 443-50, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25766917

RESUMO

Three new diphenyl ether derivatives, talaromycins A-C (1-3, resp.), together with six known analogs, 4-9, were isolated from a gorgonian-derived fungus, Talaromyces sp. The structures of the new compounds were determined by analysis of extensive NMR spectroscopic data. All of the isolated metabolites, 1-9, were evaluated for their cytotoxic and antifouling activities. Compound 4 exhibited pronounced cytotoxicity against the tested human cell lines with the IC50 values ranging from 4.3 to 9.8 µM. Compounds 3, 5, 8, and 9 showed potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite with the EC50 values ranging from 2.2 to 4.8 µg/ml.


Assuntos
Éteres Fenílicos/química , Éteres Fenílicos/farmacologia , Talaromyces/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Biofilmes/efeitos dos fármacos , Incrustação Biológica , Linhagem Celular Tumoral , Humanos , Éteres Fenílicos/isolamento & purificação , Polienos/química , Polienos/isolamento & purificação , Polienos/farmacologia , Salicilatos/química , Salicilatos/isolamento & purificação , Salicilatos/farmacologia , Compostos de Espiro/química , Compostos de Espiro/isolamento & purificação , Compostos de Espiro/farmacologia , Thoracica/efeitos dos fármacos , Thoracica/fisiologia
15.
J Agric Food Chem ; 62(50): 12103-11, 2014 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-25383633

RESUMO

A high-resolution gas chromatography/mass spectrometry (GC/MS) with selected ion monitor method focusing on the characterization and quantitative analysis of ginkgolic acids (GAs) in Ginkgo biloba L. plant materials, extracts, and commercial products was developed and validated. The method involved sample extraction with (1:1) methanol and 10% formic acid, liquid-liquid extraction with n-hexane, and derivatization with trimethylsulfonium hydroxide (TMSH). Separation of two saturated (C13:0 and C15:0) and six unsaturated ginkgolic acid methyl esters with different positional double bonds (C15:1 Δ8 and Δ10, C17:1 Δ8, Δ10, and Δ12, and C17:2) was achieved on a very polar (88% cyanopropyl) aryl-polysiloxane HP-88 capillary GC column. The double bond positions in the GAs were determined by ozonolysis. The developed GC/MS method was validated according to ICH guidelines, and the quantitation results were verified by comparison with a standard high-performance liquid chromatography method. Nineteen G. biloba authenticated and commercial plant samples and 21 dietary supplements purported to contain G. biloba leaf extracts were analyzed. Finally, the presence of the marker compounds, terpene trilactones and flavonol glycosides for Ginkgo biloba in the dietary supplements was determined by UHPLC/MS and used to confirm the presence of G. biloba leaf extracts in all of the botanical dietary supplements.


Assuntos
Suplementos Nutricionais/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ginkgo biloba/química , Extratos Vegetais/química , Salicilatos/química , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Salicilatos/isolamento & purificação
16.
J Nat Prod ; 77(9): 1987-91, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25084548

RESUMO

Antileishmanial bioassay guided fractionation of Geosmithia langdonii has resulted in the isolation and identification of two new compounds (1 and 2) together with 10 known compounds (3-12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as mass spectrometry. The absolute configuration at C4, C5, and C6 of 2 was determined as R using a modified Mosher esterification method and NOESY correlations. The extracts and the isolated metabolites were evaluated for their antileishmanial activities. Compounds 3, 9, 11, and 12 were found to be active against Leishmania donovani with IC50 values of 6.9, 3.3, 8.5, and 9.2 µM, respectively, while compounds 1, 5, and 10 showed lower activities against L. donovani with IC50 values of 13.0, 47.3, and 34.0 µM, respectively.


Assuntos
Compostos Benzidrílicos/isolamento & purificação , Compostos Benzidrílicos/farmacologia , Cicloexanonas/isolamento & purificação , Cicloexanonas/farmacologia , Hypocreales/química , Leishmania donovani/efeitos dos fármacos , Salicilatos/isolamento & purificação , Salicilatos/farmacologia , Antineoplásicos Fitogênicos/química , Aspergillus fumigatus/efeitos dos fármacos , Compostos Benzidrílicos/química , Candida/efeitos dos fármacos , Cicloexanonas/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Complexo Mycobacterium avium/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Salicilatos/química
17.
Phytomedicine ; 21(7): 960-5, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24703325

RESUMO

Syzygium tetragonum Wall is a Chinese folk medicine for the treatment of rheumatism, joint swelling and pain. By High Content Screening (HCS), 8 compounds (1-8) from Syzygium tetragonum Wall were evaluated for their inhibitory activity on the nuclear translocation of NFATc1 in EGFP-NFATc1 U2OS cells. Among them, 6-[10'(Z)-heptadecenyl] salicylic acid (8) exhibited a significant inhibitory activity. In RAW 264.7 cells, it could dose-dependently prevent nuclear NFATc1 translocation induced by receptor activator of nuclear factor κB ligand (RANKL). The differentiation of osteoclasts from bone marrow derived macrophages (BMMs) was significantly inhibited by 8 in a dose-dependent manner. The mRNA expression of TRAP, CtsK, and MMP9, key enzymes for the bone resorption secreted by osteoclasts, were also significantly down-regulated; and MMP9 activity was also obviously decreased. More importantly, the bone resorption activity of osteoclasts was dose-dependently suppressed by compound 8. Our results suggest that compound 8 can effectively inhibit osteoclastogenesis and bone erosion via preventing NFATc1 nuclear translocation and might be a promising drug candidate for relevant diseases.


Assuntos
Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Salicilatos/farmacologia , Syzygium/química , Fosfatase Ácida/genética , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Reabsorção Óssea/genética , Catepsina K/genética , Linhagem Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Isoenzimas/genética , Macrófagos/efeitos dos fármacos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional Chinesa , Camundongos Endogâmicos BALB C , Estrutura Molecular , Osteoclastos/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/química , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Salicilatos/isolamento & purificação , Fosfatase Ácida Resistente a Tartarato
18.
ACS Chem Biol ; 8(12): 2635-42, 2013 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-24143955

RESUMO

Conjugation of small ubiquitin-like modifier (SUMO) to protein (SUMOylation) regulates multiple biological systems by changing the functions and fates of a large number of proteins. Consequently, abnormalities in SUMOylation have been linked to multiple diseases, including breast cancer. Using an in situ cell-based screening system, we have identified spectomycin B1 and related natural products as novel SUMOylation inhibitors. Unlike known SUMOylation inhibitors such as ginkgolic acid, spectomycin B1 directly binds to E2 (Ubc9) and selectively blocks the formation of the E2-SUMO intermediate; that is, Ubc9 is the direct target of spectomycin B1. Importantly, either spectomycin B1 treatment or Ubc9 knockdown inhibited estrogen-dependent proliferation of MCF7 human breast-cancer cells. Our findings suggest that Ubc9 inhibitors such as spectomycin B1 have potential as therapeutic agents against hormone-dependent breast cancers.


Assuntos
Regulação Neoplásica da Expressão Gênica , Processamento de Proteína Pós-Traducional , Espectinomicina/farmacologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Linhagem Celular Tumoral , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Cinética , Ligação Proteica , Salicilatos/química , Salicilatos/isolamento & purificação , Salicilatos/farmacologia , Transdução de Sinais , Espectinomicina/química , Sumoilação , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/genética
19.
J Enzyme Inhib Med Chem ; 28(3): 565-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22380770

RESUMO

Fatty acid synthase (FAS) has been proposed to be a new drug target for the development of anticancer agents because of the significant difference in expression of FAS between normal and tumour cells. Since a n-hexane-soluble extract from Ginkgo biloba was demonstrated to inhibit FAS activity in our preliminary test, we isolated active compounds from the n-hexane-soluble extract and evaluated their cytotoxic activity in human cancer cells. Three ginkgolic acids 1-3 isolated from the n-hexane-soluble extract inhibited the enzyme with IC(50) values 17.1, 9.2 and 10.5 µM, respectively, and they showed cytotoxic activity against MCF-7 (human breast adenocarcinoma), A549 (human lung adenocarcinoma) and HL-60 (human leukaemia) cells. Our findings suggest that alkylphenol derivatives might be a new type of FAS inhibitor with cytotoxic activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidores Enzimáticos/farmacologia , Ácido Graxo Sintases/antagonistas & inibidores , Ginkgo biloba/química , Salicilatos/farmacologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Antineoplásicos Fitogênicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Feminino , Células HL-60/efeitos dos fármacos , Hexanos/química , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Salicilatos/química , Salicilatos/isolamento & purificação
20.
Int J Mol Sci ; 13(11): 14707-22, 2012 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-23203090

RESUMO

The aim of this study was to investigate the chemical composition of acetone extracts of the lichens Toninia candida and Usnea barbata and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts together with some of their major metabolites. The chemical composition of T. candida and U. barbata extracts was determined using HPLC-UV analysis. The major phenolic compounds in these extracts were norstictic acid (T. candida) and usnic acid (U. barbata). Antioxidant activity was evaluated by free radical scavenging, superoxide anion radical scavenging, reducing power and determination of total phenolic compounds. Results of the study proved that norstictic acid had the largest antioxidant activity. The total content of phenols in the extracts was determined as the pyrocatechol equivalent. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration using the broth microdilution method. The most active was usnic acid with minimum inhibitory concentration values ranging from 0.0008 to 0.5 mg/mL. Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using the microculture tetrazolium test. Usnic acid was found to have the strongest anticancer activity towards both cell lines with IC(50) values of 12.72 and 15.66 µg/mL.


Assuntos
Benzofuranos/farmacologia , Lactonas/farmacologia , Líquens/química , Salicilatos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Ascomicetos/química , Bactérias/efeitos dos fármacos , Benzofuranos/química , Benzofuranos/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fungos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Lactonas/química , Lactonas/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenóis , Picratos/antagonistas & inibidores , Salicilatos/química , Salicilatos/isolamento & purificação , Usnea/química
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