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1.
J Environ Pathol Toxicol Oncol ; 38(3): 217-227, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679309

RESUMO

BACKGROUND: Natural active components have been reported to serve as adjuvant medications in the clinical practice of cancer therapeutics. However, the antineoplastic roles of atractylenolide III (ATL) are rarely reported. In the present study, we assessed the functions of ATL combined with docetaxel in gastric cancer cells. METHODS: Cell viability and cytotoxic activity were evaluated using CCK-8 and LDH-based cytotoxicity assays, respectively. Protein expression levels were measured by western blotting analysis. Annexin V-FITC/PI staining was used to evaluate cell apoptosis using flow cytometry. RESULTS: AGS and SGC-7901 cell viability was significantly inhibited in ATL combined with docetaxel group compared with docetaxel treatment alone. The levels of LDH, apoptosis rate, and the ratio of BAX to Bcl-2 were significantly elevated in combination treatment group compared to docetaxel treatment alone. Intriguingly, docetaxel combined with ATL resulted in a significant decrease in FGFR1, FGFR2, and FGFR4 protein expression compared with docetaxel treatment alone. Knockout of FGFR1, -2, and -4 exhibited a similar role of medications to inhibit growth and induce apoptosis in AGS and SGC-7901 cells. CONCLUSIONS: ATL and docetaxel treatment performed the synergistic effects on the inhibition of growth and induction of apoptosis in gastric cancer cells, and the underlying mechanism was mediated, at least partially, through the inhibition of FGFR1, -2, and -4.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Lactonas/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Sesquiterpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias Gástricas/tratamento farmacológico
2.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3672-3683, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602939

RESUMO

Sesquiterpenes are a class of terpenoids composed of three isoprene units( 15 carbons). Sesquiterpenoids possess a variety of different structures,including acyclic sesquiterpenes,monocyclic sesquiterpenoids,bicyclic sesquiterpenoids,tricyclic sesquiterpenoids,tetracyclic sesquiterpenoids and macrocyclic sesquiterpenoids. Among them,a large number of monocyclic sesquiterpenoids were isolated and display extensive bioactivities,such as cytotoxic,antioxidant,anti-inflammatory,antibacterial and other activities. In this review,we summarized the progress about the phytochemistry and biological activities of monocyclic sesquiterpenoids( a total of161 compounds) reported from 2014 to 2018( 5 years),including megastigmanes,monocyclofarnesol-type,bisabolane-type,germacrane-type,and other types of monocyclic sesquiterpenoids. Furthermore,several future research perspectives and development of sesquiterpenoids as potential therapeutic agents were discussed as well.


Assuntos
Sesquiterpenos/farmacologia , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Estrutura Molecular
3.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3684-3694, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602940

RESUMO

Pistacia lentiscus,which belongs to foreign medicine resources,is widely distributed in the Mediterranean and Middle Eastern area. The essential oils are a mixture of several volatile compounds mainly monoterpenes and sesquiterpenes obtained from different parts of P. lentiscus by hydrodistillation. The variability of chemical composition,biological activities and content of essential oil is strongly affected by extraction technology,environmental and sex factors. It is indicated that essential oils of P. lentiscus have kinds of biological activities such as antibacterial,anticancer,anti-atherogenesis,antioxidant,anti-inflammatory and insecticidal activities.Many scholars hold the opinion that combination of different components with synergistic and/or additive actions should account for their biological activities. Due to its diverse efficacy and special taste,the essential oil of P. lentiscus has been extensively used in medicine,food and cosmetics industries. A mini review of chemical constituents and biological activities of essential oil of P. lentiscus in the past20 years is made here to provide valuable reference for the construction of " the Belt and Road".


Assuntos
Óleos Voláteis/química , Óleos Voláteis/farmacologia , Pistacia/química , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Monoterpenos/química , Monoterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia
4.
J Chem Phys ; 151(12): 125103, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575200

RESUMO

This article reports on a frequency domain analysis of quasielastic neutron scattering spectra from free and Huperzine-A-inhibited human acetylcholinesterase, extending a recent time domain analysis of the same experimental data [M. Saouessi et al., J. Chem. Phys. 150, 161104 (2019)]. An important technical point here is the construction of a semianalytical model for the resolution-broadened dynamic structure factor that can be fitted to the experimental spectra. We find comparable parameters as in our previous study and demonstrate that our model is sensitive to subpercent changes in the experimental data, which are caused by reversible binding of the inhibitor Huperzine A.


Assuntos
Acetilcolinesterase/química , Alcaloides/química , Inibidores da Colinesterase/química , Sesquiterpenos/química , Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Humanos , Difração de Nêutrons , Domínios Proteicos , Sesquiterpenos/farmacologia
5.
J Agric Food Chem ; 67(38): 10646-10652, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31479255

RESUMO

A new monosesquiterpene diacetylgliocladic acid (1), a new dimeric sesquiterpene divirensol H (9), and two exceptionally novel trimeric sesquiterpene trivirensols A and B (11 and 12), together with another eight known congeners, were purified from an endophytic fungus Trichoderma virens FY06, derived from Litchi chinensis Sonn. whose fruit is a delicious and popular food. All of them were identified by comprehensive spectroscopic analysis, combined with biosynthetic considerations. Trivirensols A and B are unprecedented trimers of which three subunits are connected by two ester bonds of the sesquiterpene class. Relative to the positive control triadimefon, all the tested metabolites showed strong inhibitory activities against at least one phytopathogenic fungus among Penicillium italicum, Fusarium oxysporum, Fusarium graminearum, Colletotrichum musae, and Colletotrictum gloeosporioides. Notably, as metabolites of the endophytic fungus from L. chinensis, they all presented strong antifungal activities against C. gloeosporioides which causes anthracnose in L. chinensis.


Assuntos
Fungicidas Industriais/farmacologia , Litchi/microbiologia , Sesquiterpenos/farmacologia , Trichoderma/química , Colletotrichum/efeitos dos fármacos , Colletotrichum/crescimento & desenvolvimento , Endófitos/química , Endófitos/genética , Endófitos/isolamento & purificação , Endófitos/metabolismo , Frutas/microbiologia , Fungicidas Industriais/química , Fungicidas Industriais/metabolismo , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Doenças das Plantas/microbiologia , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Trichoderma/genética , Trichoderma/isolamento & purificação
6.
Life Sci ; 236: 116867, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520598

RESUMO

AIM: Cyclophosphamide (CP) is a potent anticancer and immunosuppressant drug. Studies have shown significant oxidative stress and cognitive impairment but neuroinflammatory and histological aberrations with its administration is underexplored. Nerolidol (NER) is a lipophilic bioactive molecule with antioxidant and anti-inflammatory properties but it has not been explored for neuroprotective potential in CP-induced neurotoxic manifestations. Therefore, in the present study, we aimed to evaluate the neuroprotective potential of NER in CP-induced neuroinflammation and associated comorbid conditions like depression and cognitive dysfunctions. MATERIALS AND METHOD: In-silico study using Schrödinger software was used to assess the binding affinity of NER with Nrf2. In the In vivo study, NER 200 and 400 mg/kg p.o. were given from 1st day to 14th day. CP 200 mg/kg, i.p., was administered on the 7th day. After 24 h of the last dosing, neurobehavioral tests like spontaneous body alternation, passive avoidance and forced swim test were performed. On completion of study, mice were sacrificed, hippocampus and cortex were removed for biochemical estimations, histopathology and immunohistochemistry of p65 NF- κB and Nrf2. KEY FINDINGS: In-silico study showed significant binding of NER into the pocket domain of Nrf2. In-vivo study showed protective effect of NER against CP-induced neuroinflammation, oxidative stress, cognitive impairment and structural abnormalities in the hippocampus and cortex regions. SIGNIFICANCE: Findings of the study suggested that NER is a potential therapeutic molecule which can mitigate CP-induced neurotoxic manifestations via Nrf2 and NF-κB pathway. However, more detailed studies are needed to explicate the mechanism underlying its neuroprotective effect.


Assuntos
Disfunção Cognitiva/prevenção & controle , Ciclofosfamida/toxicidade , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imunossupressores/toxicidade , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Fármacos Neuroprotetores , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Transdução de Sinais
7.
Life Sci ; 233: 116732, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31394125

RESUMO

AIMS: Linderane, an important bioactive compound in Linderae, improved glucose and lipid metabolism in ob/ob mice. However, the effect of linderane on streptozotocin (STZ)-induced oxidative damage in INS-1 cells remains unclear. MAIN METHODS: INS-1 cells were pre-treated with different doses of linderane for 2 h and then treated with 3 mM STZ for 12 h. Cell viability was determined by MTT assay. Cell apoptosis was detected using an Annexin V-FITC Apoptosis Detection Kit. The level of intracellular ROS was determined using dichlorofluorescein-diacetate (DCFH-DA). The activities of insulin secretion, SOD, catalase (CAT) and GPx were measured using ELISA kits. The expression levels of bax, bcl-2, p38, p-p38, nuclear Nrf2 and HO-1 were measured using western blot. KEY FINDINGS: The results showed that STZ-caused inhibitory effects on cell viability and insulin secretion were mitigated by linderane. Furthermore, linderane inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, linderane suppressed the activation of p38 MAPK pathway, as well as enhanced the activation of Nrf2 pathway in STZ-induced INS-1 cells. Activation of p38 MAPK pathway or inhibition of Nrf2 significantly reversed the protective effects of linderane against STZ-induced ROS production and cell apoptosis. SIGNIFICANCE: The protective effects of linderane on STZ-induced INS-1 cells might be attributed to the inhibition of p38 MAPK and activation of Nrf2 pathway.


Assuntos
Apoptose/efeitos dos fármacos , Furanos/farmacologia , Insulina/metabolismo , Insulinoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Estreptozocina/toxicidade , Animais , Insulinoma/metabolismo , Insulinoma/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ratos , Células Tumorais Cultivadas
8.
Life Sci ; 233: 116750, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31408659

RESUMO

AIM: Rheumatoid arthritis (RA) is the most widespread inflammatory arthropathy, which causes severe disability. It is highly important to ameliorate the side effects caused by different drugs used to treat RA. Therefore, this study assessed the potential role of ß-caryophyllene (BCP) in treating adjuvant-induced arthritis (AIA), increasing the efficacy of methotrexate (MTX) and/or leflunomide (LEF), and ameliorating their side effects. MATERIAL AND METHODS: AIA was induced in rats by injecting complete Freund's adjuvant. The rats were divided into different groups such as sham group; control group; monotherapy groups, including BCP (300 mg/kg), MTX (1 mg/kg), and LEF (10 mg/kg); and combined groups, including MTX + BCP, LEF + BCP, MTX + LEF, and MTX + LEF + BCP groups. KEY FINDINGS: Monotherapy with BCP or MTX or LEF as well as MTX + LEF significantly reduced paw thickness and arthritic index; the histopathological changes in hind paw joints were recovered; and oxidative stress and tumor necrosis factor-alpha (TNF-α) levels in arthritic rats were reduced. The co-administration of BCP and MTX and/or LEF significantly improved the therapeutic efficacy of MTX and/or LEF and significantly reduced the myelosuppressive and hepatotoxic effects of MTX and/or LEF. Taken together, BCP could be used with MTX and/or LEF for the treatment of RA to reduce the side effects of the drugs and increase their efficacy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Artrite Experimental/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Imunossupressores/administração & dosagem , Leflunomida/administração & dosagem , Metotrexato/administração & dosagem , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antimetabólitos Antineoplásicos/efeitos adversos , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Quimioterapia Combinada , Imunossupressores/efeitos adversos , Leflunomida/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Ratos , Ratos Wistar , Sesquiterpenos/administração & dosagem
9.
Zhonghua Fu Chan Ke Za Zhi ; 54(7): 464-469, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31365959

RESUMO

Objective: To evaluate the effects of parthenolide on estradiol-synthesizing enzyme, steroidogenic acute regulatory protein (StAR), and ER isoforms,VEGF in human endometriotic stromal cells. Methods: Primary endometriotic stromal cells were treated with different concentrations (1, 5, 10 and 20 µmol/L) of parthenolide. The mRNA of StAR, ER isoforms (ERα and ERß), PR, vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumour necrosis factor-α (TNFα), tumour necrosis factor receptor (TNFR) 1, TNFR2 were measured by real-time PCR. The levels of estradiol and progesterone in the cell supernatant were measured by ELISA. Results: Different concentrations of parthenolide could up-regulate the mRNA of StAR in primary endometriotic stromal cells (F=5.722, P<0.05); the mRNA of StAR in the group of 20 µmol/L was significantly higher than that of the control group [2.6±0.3 versus 1.0, P<0.01]. Different concentrations of parthenolide could down-regulate the mRNA of ERα (F=6.921, P<0.01); the mRNA of ERα in the group of 20 µmol/L and 10 µmol/L were significantly lower than those of the control group [0.2±0.3 versus 0.3±0.3 versus 1.0, all P<0.05]. Different concentrations of parthenolide could down-regulate the ratios of ERα/ERß mRNA levels (F=4.209, P<0.05). Different concentrations of parthenolide could up-regulate the mRNA of VEGF and TNFR1 (F=10.964, P<0.01; F=7.286, P<0.01). There were no statiscal significances with different concentrations of parthenolide on the mRNA of ERß, PR, IL-6, TNFα and TNFR2, and the levels of estradiol and progesterone in the cell supernatant (all P>0.05). Conclusions: Parthenolide may regulate the expression of estradiol-synthesizing enzyme, ER isoforms and angiogenesis in endometriotic stromal cells. Parthenolide may promote the development of endometriosis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Endometriose , Endométrio/efeitos dos fármacos , Sesquiterpenos/farmacologia , Células Estromais/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endometriose/induzido quimicamente , Endometriose/genética , Endométrio/metabolismo , Endométrio/patologia , Estradiol , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Isoformas de Proteínas , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Pestic Biochem Physiol ; 159: 59-67, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400785

RESUMO

Phytophthora capsici is a plant oomycete pathogen, which causes many devastating diseases on a broad range of hosts. Zedoary turmeric oil (ZTO) is a kind of natural plant essential oil that has been widely used in pharmaceutical applications. However, the antifungal activity of ZTO against phytopathogens remains unknown. In this study, we found ZTO could inhibit P. capsici growth and development in vitro and in detached cucumber and Nicotiana benthamiana leaves. Besides, ZTO treatment resulted in severe damage to the cell membrane of P. capsici, leading to the leakage of intracellular contents. ZTO also induced a significant increase in relative conductivity, malondialdehyde concentration and glycerol content. Furthermore, we identified 50 volatile organic compounds from ZTO, and uncovered Curcumol, ß-elemene, curdione and curcumenol with strong inhibitory activities against mycelial growth of P. capsici. Overall, our results not only shed new light on the antifungal mechanism of ZTO, but also imply a promising alternative for the control of phytophthora blight caused by P. capsici.


Assuntos
Antifúngicos/farmacologia , Membrana Celular/efeitos dos fármacos , Óleos Voláteis/farmacologia , Phytophthora/efeitos dos fármacos , Extratos Vegetais/farmacologia , Óleos Vegetais/farmacologia , Curcuma , Phytophthora/metabolismo , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/farmacologia
11.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2274-2277, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359653

RESUMO

Two sesquiterpenes were isolated from the agarwood originating from Gyrinops salicifolia with various chromatographic techniques, and their structures were determined as 12-hydroxy-dihydrocyperolone(1) and(rel)-4ß,5ß,7ß-eremophil-9-en-12,8α-olide(2), through a combined analysis of physicochemical properties and spectroscopic evidence. Compound 1 was a new compound. Compound 2 showed cytotoxicities against K562 and BEL-7401 cell lines, with IC_(50) values of(17.85±0.04) and(21.82±0.07) mg·L~(-1), respectively [taxol as positive control, with IC_(50) values of(1.97±0.11) and(6.31±0.08) mg·L~(-1)].


Assuntos
Sesquiterpenos/farmacologia , Thymelaeaceae/química , Madeira/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/isolamento & purificação
12.
Phytochemistry ; 166: 112054, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31284174

RESUMO

Eremophila bignoniiflora is a shrub distributed throughout inland northern and eastern Australia, and it has been used in several medicinal applications by some Australian Aboriginal people. In our continued search for anti-diabetic constituents from natural resources, the crude ethyl acetate extract of E. bignoniiflora was found to have protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity with an IC50 value of 23.9 ±â€¯1.9 µg/mL. High-resolution PTP1B inhibition profiling combined with HRMS and NMR were subsequently used to investigate the individual compounds responsible for the observed bioactivity of the crude extract. This led to identification of five undescribed 2(5H)-furanone sesquiterpenes, together with 13 flavonoids and phenolic compounds. Dose-response curves of the isolated compounds revealed that two 2(5H)-furanone sesquiterpene cinnamates and three flavonoids exhibited moderate PTP1B inhibitory activity with IC50 values from 41.4 ±â€¯1.4 to 154.5 ±â€¯8.9 µM.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Furanos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Scrophulariaceae/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia
13.
J Chem Ecol ; 45(8): 684-692, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31289990

RESUMO

Herbivore-induced plant volatiles (HIPVs) are important cues for natural enemies to find their hosts. HIPVs are usually present as blends and the effects of combinations of individual components are less studied. Here, we investigated plant volatiles in a tritrophic system, comprising the parasitoid wasp Lytopylus rufipes Nees (Hymenoptera: Braconidae), the Oriental fruit moth Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and Japanese pear, Pyrus pyrifolia 'Kosui', so as to elucidate the effects of single components and blends on wasp behaviors. Bioassays in a four-arm olfactometer, using either shoots or their isolated volatiles collected on adsorbent, revealed that female wasps preferred volatiles from host-infested shoots over those from intact shoots. Analyses identified (Z)-3-hexenyl acetate (H), linalool (L), (E)-ß-ocimene (O), (E)-3,8-dimethyl-1,4,7-nonatriene (D), and (E,E)-α-farnesene (F). Among them, only F was induced by infestation with G. molesta. When tested singly, only O and D elicited positive responses by L. rufipes. Binary blends of HO and DF elicited a positive response, but that of HD elicited a negative one, even though D alone elicited a positive response. Remarkably, wasps did not prefer either the ODF or HL blends, but showed a highest positive response to a quinary blend (HLODF). These results show that synergism among volatiles released from host-infested plants is necessary for eliciting high behavioral responses in L. rufipes, enabling L. rufipes to find its host efficiently.


Assuntos
Comportamento de Busca por Hospedeiro/efeitos dos fármacos , Pyrus/química , Compostos Orgânicos Voláteis/farmacologia , Vespas/fisiologia , Alcenos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Herbivoria , Mariposas/fisiologia , Brotos de Planta/química , Brotos de Planta/metabolismo , Brotos de Planta/parasitologia , Pyrus/metabolismo , Pyrus/parasitologia , Sesquiterpenos/farmacologia , Compostos Orgânicos Voláteis/química
14.
Chemistry ; 25(54): 12644-12651, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31310394

RESUMO

The illudin natural product family are fungal secondary metabolites with a characteristic spirocyclopropyl-substituted fused 6,5-bicyclic ring system. They have been extensively studied for their cytotoxicity in various tumor cell types, and semisynthetic derivatives with improved therapeutic characteristics have progressed to clinical trials. Although it is believed that this potent alkylating compound class acts mainly through DNA modification, little is known about its binding to protein sites in a cellular context. To reveal putative protein targets of the illudin family in live cancer cells, we employed a semisynthetic strategy to access a series of illudin-based probes for activity-based protein profiling (ABPP). While the probes largely retained potent cytotoxicity, proteomic profiling studies unraveled multiple protein hits, suggesting that illudins exert their mode of action not from addressing a specific protein target but rather from DNA modification and unselective protein binding.


Assuntos
Proteínas/química , Proteoma/química , Sesquiterpenos/farmacologia , Compostos de Espiro/farmacologia , Células A549 , Alquilação , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Sobrevivência Celular , Humanos , Ligação Proteica , Proteínas/metabolismo , Proteoma/metabolismo , Metabolismo Secundário , Sesquiterpenos/química , Compostos de Espiro/química
15.
Fitoterapia ; 137: 104243, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226283

RESUMO

Two new sesquiterpenoids, leptosphins A (1) and B (2), and a new cyclopiane diterpene, leptosphin C (3), along with four known diterpenes (4-7) were isolated from the solid fermentation cultures of an endophytic fungus Leptosphaeria sp. XL026 isolated from the leaves of Panax notoginseng. Their structures were elucidated by extensive spectroscopic methods and single-crystal X-ray diffraction (data). Compound 1 represents the first sulfur-containing eremophilane sesquiterpene. Compounds 5 and 7 displayed medium antifungal activity against Rhizoctonia cerealis, as well as 6 against Verticillium dahliae Kleb with an MIC value of 12.5 µg/mL. Furthermore, compounds 2, 5, 6 and 7 showed medium antibacterial activity against Bacillus cereus with MIC values of 12.5-6.25 µg/mL, as well as 6 also against Pseudomonas aeruginosa with an MIC value of 12.5 µg/mL.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Ascomicetos/química , Diterpenos/farmacologia , Panax notoginseng/microbiologia , Sesquiterpenos/farmacologia , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , China , Diterpenos/isolamento & purificação , Estrutura Molecular , Folhas de Planta/microbiologia , Sesquiterpenos/isolamento & purificação
16.
Fitoterapia ; 137: 104247, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31247217

RESUMO

A new sesquiterpene glycoside and a new amide have been isolated from the stems of Tinospora sinensis. Their structures were established by 2D NMR spectroscopic techniques (1H,1H-COSY, NOESY, HSQC and HMBC) and mass spectrometry. The isolated compounds were subjected to evaluate neuroprotective activities in vitro. The pre-treatment of two new compounds can significantly ameliorate damage of oxidative stress induced by Aß25-35 and improve PC12 cells survival.


Assuntos
Amidas/farmacologia , Glicosídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Tinospora/química , Amidas/isolamento & purificação , Animais , Glicosídeos/isolamento & purificação , Estrutura Molecular , Células PC12 , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/isolamento & purificação , Tibet
17.
Food Chem ; 295: 16-25, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31174745

RESUMO

The instability of Laurel essential oil (LEO) and easy leakage of silver nanoparticle (AgNP) restricts their application in food field. To control their release, liposomes were used to encapsulate LEO and AgNPs (Lip-LEO-AgNPs), and mixed with chitosan to coat polyethylene (PE) films (PC-Lip/LEO/AgNPs) to package pork. The results show that only about 29.30% of LEO and 11.79% of AgNPs were released from the liposome after 7 days at 25 °C. Nevertheless, Lip-LEO-AgNPs showed good antioxidant properties. Moreover, PC-Lip/LEO/AgNPs films had good antimicrobial activity. Evaluation tests on pork indicate that PC-Lip/LEO/AgNPs films could keep the quality of pork at 4 °C for 15 days while pure PE film only kept it for 9 days, and that the coating films had no cytotoxicity. PC-Lip/LEO/AgNPs films exhibited significant combined action in functional packaging to extend storage period, and provided a new idea for the application of LEO and AgNPs in food.


Assuntos
Conservação de Alimentos/métodos , Lipossomos/química , Óleos Voláteis/química , Carne Vermelha , Sesquiterpenos/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Quitosana/química , Qualidade dos Alimentos , Armazenamento de Alimentos/métodos , Humanos , Lipossomos/farmacologia , Nanopartículas Metálicas/química , Óleos Voláteis/farmacologia , Tamanho da Partícula , Sesquiterpenos/farmacologia , Prata/química , Suínos , Temperatura Ambiente
18.
Chem Biol Interact ; 309: 108703, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31194954

RESUMO

ß-2-himachalen-6-ol (HC), a major sesquiterpene isolated from the Lebanese wild carrot umbels, was shown to possess remarkable in vitro and in vivo anticancer activities. The present study investigates the anti-metastatic activity of HC post 4T1 breast cancer cells inoculation in a murine model. The effect of HC on 4T1 cell viability was assessed using WST-1 kit, while cell cycle analysis was performed using flow cytometry. Tumor development and metastasis were evaluated by injecting 4T1 cells in the mice mammary gland region followed by either HC or cisplatin treatment. The 6-thioguanine assay was used for the quantification of metastatic cells in the blood. HC treatment caused a dose-dependent decrease in cell viability with IC50 and IC90 values of 7 and 28 µg/mL respectively. Concomitant treatment with cisplatin significantly reduced cell viability when compared to cells treated with cisplatin or HC alone. Flow cytometry revealed a significant increase (p˂0.05) in cell count in the Sub-G1 phase at HC 10 µg/mL, and total DNA fragmentation (p˂0.001) at HC 25 µg/mL. Annexin/PI staining showed early and late apoptotic mode of cell death upon treatment with HC. Histopathological evaluation revealed less incidence of primary and metastatic tumor/inflammation in the HC and cisplatin treated groups. Tumor size and colony-forming units were significantly decreased in the HC treated group. HC treatment induced cell cycle arrest, promoted apoptosis and reduced the incidence of primary and metastatic lesions caused by 4T1 cells. The present findings suggest that HC has an anti-metastatic potential against aggressive types of cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Sesquiterpenos/uso terapêutico , Pele/patologia , Transplante Homólogo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
19.
Phytochemistry ; 165: 112047, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203102

RESUMO

Four undescribed lignans and two undescribed sesquiterpenic acids, together with three known compounds (hypochoeroside C, hypochoeroside D, and 5-O-caffeoylshikimic acid) were isolated from the roots of Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). The lignans were identified as 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranosyl-2'-O-methacrylate, (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one, and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid. The two sesquiterpenic acids were identified as the ring open precursors of hypochoerosides C and D. Structures were elucidated using NMR and HRMS. Absolute configurations of (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid were determined using electronic circular dichroism (ECD) spectroscopy. 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside was evaluated for its anti-proliferative activity against myeloma cell lines MM1S, U266, and NCI-H929 and showed cytotoxicity at 100 mM against MM1S strain. No neurotoxicity was observed for major compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, and hypochoeroside D in a fluorescence assay measuring neurite outgrowth in dorsal root ganglion (DRG) neurons. Additionally, compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, hypochoeroside D, and hypochoerosidic acid D were quantified in unstressed and drought-stressed plants using HPLC-DAD. Drought-stressed plants were found to contain lower concentrations of the lignan 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside and sesquiterpene lactone hypochoeroside C.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Lactonas/farmacologia , Lignanas/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Mieloma Múltiplo/patologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
20.
Phytochemistry ; 164: 154-161, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31151062

RESUMO

Oxytropiols A-J, ten undescribed guaiane-type sesquiterpenoids, and the mycotoxin swainsonine (SW) were isolated from the locoweed endophytic fungus Alternaria oxytropis. The chemical structures of these sesquiterpenoids were elucidated on the basis of HR-ESI-MS and NMR data including 1H, 13C, HSQC, 1H-1H COSY, HMBC, and NOESY spectra, and the absolute configurations of these compounds were determined using a modified Mosher's method and X-ray diffraction spectroscopy. A possible biosynthetic pathway of these guaiane-type sesquiterpenoids is discussed, and proposed that post-modification oxidative enzymes might form these highly polyhydroxylated structures. Compound 1 displayed biological effects on the root growth of Arabidopsis thaliana, and SW displayed cytotoxicity against A549 and HeLa cancer cell lines.


Assuntos
Alternaria/química , Antineoplásicos/farmacologia , Micotoxinas/farmacologia , Sesquiterpenos/farmacologia , Swainsonina/farmacologia , Células A549 , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Modelos Moleculares , Conformação Molecular , Micotoxinas/química , Micotoxinas/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade , Swainsonina/química , Swainsonina/isolamento & purificação
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