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1.
Chem Pharm Bull (Tokyo) ; 68(1): 96-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902905

RESUMO

Chemical investigation of the aerial parts of Andrographis paniculata resulted in isolation of nine compounds, including a new ent-labdane diterpenoid, andrographic acid methyl ester (1), a new chalcone glucoside, pashanone glucoside (5), and seven known metabolites, andrograpanin (2), andrographolide (3), andropanolide (4), andrographidine A (6), andrographidine F (7), 6-epi-8-O-acetyl-harpagide (8), and curvifloruside F (9). Their chemical structures were elucidated based on comprehensive analyses of the spectroscopic data, including NMR and MS. Among the isolated compounds, andropanolide exerted cytotoxicity toward LNCaP, HepG2, KB, MCF7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 31.8 to 45.9 µM. In addition, andropanolide significantly inhibited the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with an IC50 value of 13.4 µM.


Assuntos
Andrographis/química , Diterpenos/química , Flavonoides/química , Andrographis/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Células RAW 264.7
2.
Fitoterapia ; 140: 104431, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759031

RESUMO

Two novel heptanornemoralisin-type diterpenoids nornemoralisins A (1) and B (2), together with two known compounds nemoralisin (3) and nemoralisin A (4), were isolated from the stem bark and leaves of Aphanamixis polystachya (Wall.) R. Parker. Their structures were established through comprehensive analyses of NMR spectroscopic data and high resolution mass spectrometric (HR-ESI-MS) data. The absolute configurations of carbon stereocenters were elucidated by circular dichroism (CD) analyses. The four compounds were tested for their potential cytotoxic effects against ACHN, HeLa, SMMC-7721, and MCF-7 cell lines. Nornemoralisins A (1) and B (2) exhibited significant cytotoxicity on ACHN with an IC50 value of 13.9 ± 0.8 and 10.3 ± 0.4 µM, respectively, and other compounds failed to reveal obvious cytotoxicity on the tested cell lines, compared to positive control vinblastine (IC50, 28.0 ± 0.9 µM).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Meliaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , China , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Folhas de Planta/química
3.
Fitoterapia ; 139: 104408, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31698058

RESUMO

One new pseudoguaianolide (1), one new megastigmane (6), and one new ent-abietane diterpene (9), together with seven known compounds (2-5, 7, 8, and 10) were isolated from the aerial parts of Euphorbia thymifolia. The structures of the new compounds and their relative configurations were determined by spectroscopic data analysis. The absolute configurations of compounds 1, 6, and 9 were determined by single-crystal X-ray crystallographic analysis, modified Mosher's method and calculated ECD experiment, respectively. All compounds were tested for their inhibitory effects against LPS-induced NO production in BV-2 microglial cells, and pseudoguaianolides (1-5) showed significant activity with IC50 values of 0.41-15.32 µM.


Assuntos
Diterpenos/farmacologia , Euphorbia/química , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Animais , Linhagem Celular Tumoral , China , Cicloexanonas , Diterpenos/isolamento & purificação , Glucosídeos , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Fármacos Neuroprotetores/isolamento & purificação , Óxido Nítrico , Norisoprenoides , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Sesquiterpenos/isolamento & purificação
4.
Fitoterapia ; 139: 104407, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31705949

RESUMO

Chemical investigations of the aerial parts of Tibetan folk medicine Delphinium chrysotrichum resulted in the isolation of two new diterpenoid alkaloids, delphatisine D (1) and chrysotrichumine A (2), together with ten known diterpenoid alkaloids (3-12) and 3ß,6α-dihydroxysclareolida (13). Delphatisine D (1) is a rare atisine-type alkaloid from genus Delphinium and is the C-15 epimer of spiramine C which bears an internal carbinolamine ether linkage (N-C-O-C) between C-7 and C-20. Chrysotrichumine A (2) is a rare natural C19-diterpenoid alkaloid possessing a nitrone group between C-17 and C-19. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 13 is a sesquiterpene first isolated from this genus. Compounds 1, 3-7 and 13 were investigated for cytotoxicity against human breast cancer cell lines of MCF-7 and MDA-MB-23, none of them presented significant activity except compound 7 which exhibited slight activity at 100 µM against MDA-MB-231, but did not reach the EC50.


Assuntos
Alcaloides/farmacologia , Delphinium/química , Diterpenos/farmacologia , Alcaloides/isolamento & purificação , Linhagem Celular Tumoral , China , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia
5.
Fitoterapia ; 139: 104414, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31705950

RESUMO

Six new triterpenoids, pseudolarins A-F (1-6), were isolated from the twigs of Pseudolarix amabilis, together with four known triterpenoids (7-10) and five known diterpenoids (11-15). Their structures were determined by extensive spectroscopic analysis, and the absolute configuration of 1 was assigned by single-crystal X-ray diffraction. Compound 1 is a 3,4:9,10-diseco-cycloartane triterpenoid possessing an unprecedented 5/5/7/6/5/6/5 ring system. Compounds 1, 5, 7, 9-11, and 13 showed inhibition against protein tyrosine phosphatase 1B (PTP1B) in vitro.


Assuntos
Diterpenos/farmacologia , Pinaceae/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Triterpenos/farmacologia , China , Diterpenos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Triterpenos/isolamento & purificação
6.
Chem Biodivers ; 16(12): e1900519, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31596057

RESUMO

A new pimarane diterpenoid, named botryopimarene A (1), was discovered from the fungus Botryotinia fuckeliana MCCC 3 A00494 isolated from the deep-sea water, together with ten known compounds. The planar structure of 1 was established based on the extensive spectroscopic analyses. The absolute configurations of tricyclic system in 1 were resolved by the theoretical ECD calculation, while the 15,16-diol moiety in the side chain was resolved by the Mo2 (OAc)4 -induced ECD spectrum. Compound 1, featuring a Δ9(11) double bond, was rarely discovered in pimarane family. Compounds 1-11 were tested for their cytotoxic activities using six human cancer cell lines by the MTT method. However, none of the compounds exhibited detectable cytotoxicities (IC50 >20 µm).


Assuntos
/química , Ascomicetos/química , Diterpenos/química , Água do Mar/microbiologia , /isolamento & purificação , Ascomicetos/isolamento & purificação , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Conformação Molecular
7.
Phytochemistry ; 168: 112113, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494343

RESUMO

Sixteen diterpenoids including nine undescribed ones, named rhodoauriculatols A-I, were isolated from the leaves of Rhododendron auriculatum Hemsl. Sixteen diterpenoids belong to seven diverse carbon skeletons, which were classified into 1,10-seco-grayanane, 1,10:2,3-diseco-grayanane, A-homo-B-nor-ent-kaurane, ent-kaurane, 4,5-seco-ent-kaurane, leucothane, and grayanane, respectively. Their structures were determined by the detailed HRESIMS, 1D and 2D NMR, UV, and IR data analysis, and their absolute configurations were established by single crystal X-ray diffraction analysis, electronic circular dichroism (ECD) data analysis, ECD calculation, as well as chemical methods. Rhodoauriculatols A-C possess a rare 1,10-seco-grayanane diterpene skeleton. Rhodoauriculatol D is the second example of the 1,10:2,3-diseco-grayanane diterpenoids, and rhodoauriculatol E is the fourth example of the A-homo-B-nor-ent-kaurane diterpenoids. Rhodomicranone E was reported as a natural product for the first time. All the isolated sixteen diterpenoids showed analgesic activities in the acetic acid-induced writhing test. Rhodoauriculatols B, E-G, rhodomicranone E, pierisformoside F, and micranthanoside A showed significant analgesic activities with the inhibition rates over 40%, and their preliminary structures-activity relationships were studied.


Assuntos
Analgésicos/farmacologia , Carbono/química , Diterpenos/farmacologia , Dor/tratamento farmacológico , Folhas de Planta/química , Rhododendron/química , Ácido Acético/antagonistas & inibidores , Ácido Acético/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Modelos Animais de Doenças , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Conformação Molecular , Medição da Dor , Relação Estrutura-Atividade
8.
Phytomedicine ; 60: 152977, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31474477

RESUMO

BACKGROUND: Intrigued by testimonies of Saxon borreliosis self-help groups concerning considerabl improvements of their symptoms by ingestion of Cistus creticus L. (Cistaceae) leaf preparations, we recently reported on the growth inhibiting activity of extracts with different polarities and its volatile oil against Borrelia burgdorferi sensu stricto (Bbss) in vitro, determined by a bioassay guided procedure. The most active volatile oil (only about 0.10% in leaves) was found to be dominated by labdane-type manoyloxides as well as carvacrol, determined via GC-MS. HYPOTHESIS: These terpenes are major active constituents of the old pharmaceutical oleoresin labdanum, which is secreted from the leaf surface of C. creticus and traditionally harvested, e.g., on Crete by brushing the shrubs. METHODS: In order to elucidate the definite anti-Borrelia active principles of C. creticus, preparative scale separation of the diethyl­ether soluble fraction of Cretan labdanum was achieved by combined silica gel 60-and RP-18 CC and analysed by novel TLC-Extractor/ES-MS as well as by 1d/2d-1H/13C-NMR data. For the antispirochaetal activity tests against Bbss in vitro, all samples were solubilised in water with addition of polysorbate 80, the effect of which on bacterial growth was examined and found to be negligible. RESULTS: This led to isolation and identification of the monoterpene carvacrol as well as of the four major manoyloxides manoyloxide (A), 3-acetoxy-manoyloxide (B), 3­hydroxy-manoyloxide (C), and epi­manoyloxide (D). Additionally, 2-keto-manoyloxide (E) and sclareol (F) were identified via GC/EI-MS. In subsequent microbiological tests of the isolated compounds, epi­manoyloxide (D) exhibited by far the strongest individual antispirochaetal effect, equal to the positive control amoxicilline. Furthermore, manoyloxide (A), carvacrol, and the diethyl­ether soluble fraction of labdanum as a whole contribute to the strong antispirochaetal activity, while the other labdanes were less active. Isolated manoyloxides were further used as external standards for a GC-MS screening of labdanum samples from different origins, revealing exceptionally high contents of all analysed manoyloxides in the samples of Cretan labdanum from C. creticus, while their contents in other commercial available labdanum samples were lower by several orders of magnitude. Especially in Spanish labdanum samples, declared as Cistus ladanifer L., mainly simple alkanes and at most traces of epi­manoyloxide (D) and of manoyloxide (A) could be detected. CONCLUSION: The application of C. creticus preparations by Lyme disease self-help groups may be considered as a reasonable therapy approach. For the first time, isolated epi­manoyloxide and carvacrol could be evaluated as most promising candidates for drug development and labdanum based phytomedicine development, respectively. They should serve as vital active markers for quality assessments of C. creticus preparations.


Assuntos
Antibacterianos/farmacologia , Borrelia/efeitos dos fármacos , Cistus/química , Diterpenos/farmacologia , Antibacterianos/isolamento & purificação , Diterpenos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Grécia , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Terpenos/isolamento & purificação , Terpenos/farmacologia
9.
Chem Biodivers ; 16(10): e1900398, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31456316

RESUMO

Phytotoxic natural products with either unique or various structures are one of the most abundant sources for the discovery of potential allelochemicals, natural herbicides, and plant growth regulators. Phytotoxic diterpenoids, a relatively large class of natural products, play an important role in the plant-plant or plant-microorganism interactions. This article argues that the phytotoxic diterpenoids isolated from the plants and microorganisms can either inhibit the seed germination and the growth of plant seedlings or lead to some disease symptoms on the tested plant tissues and plant seedlings.


Assuntos
Produtos Biológicos/farmacologia , Diterpenos/farmacologia , Compostos Fitoquímicos/farmacologia , Plantas/química , Plântula/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Plantas/efeitos dos fármacos , Plantas/microbiologia
10.
Chem Biodivers ; 16(10): e1900443, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468670

RESUMO

Chronic myelogenous leukemia (CML) is a disease of the blood stem cells that features the oncoprotein Bcr-Abl. Tyrosine kinase inhibitors (TKIs) are used to treat CML patients, but these have limited efficacy due to the emergence of resistance via genetic mutation. Kamebakaurin is an ent-kaurane diterpenoid that has been isolated from Rabdosia excisa (Maxim.) H.Hara. Herein, we investigate the potential of kamebakaurin as a chemotherapy reagent for the treatment of CML. We conducted in vitro and in vivo biological experiments and found that kamebakaurin potently inhibits cell proliferation, mainly by enhancing cell apoptosis and down-regulating Bcr-Abl protein levels. In addition, kamebakaurin was found to inhibit tumor growth and has no side effects on five internal organs for in vivo experiment. These results suggest that kamebakaurin is a potential anticancer agent and is a key compound for further investigations.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diterpenos/farmacologia , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Isodon/química , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Conformação Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Relação Estrutura-Atividade
11.
J Toxicol Sci ; 44(8): 523-533, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31378763

RESUMO

Stephanthraniline A (STA) is a C21 steroidal aglycone isolated from the stem of Stephanotis mucronata (Blanco) Merr. that exerts growth inhibition in human colon cancer cells. However, the intracellular molecular mechanisms whereby this occurs have not been well characterized. In this study, we found that STA significantly inhibits the growth of HCT116 colon cancer cells in a time- and concentration-dependent manner. The inhibitory effect of STA on cell growth was related to the induction of apoptosis. Activated caspase-3, caspase-8 and caspase-9, along with a decreased Bcl-2/Bcl-x ratio and loss of mitochondrial membrane potential (Δψm), were observed in response to STA treatment. Furthermore, treatment of HCT116 cells with STA resulted in G0/G1 phase cell cycle arrest accompanied by decreased mRNA levels of cyclin-dependent kinase 4 (CDK4), p21 and c-myc. Additionally, the inhibition of Akt signaling and activation of p38 signaling were observed after treatment with STA in HCT116 cells. These findings indicate that STA inhibits HCT116 cell growth by promoting apoptosis, the dysregulation of mitochondrial function, and cell cycle arrest.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Diterpenos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
12.
Molecules ; 24(13)2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31284657

RESUMO

Two new 11,20-epoxybriaranes, fragilides P (1) and Q (2), as well as two known analogues, robustolide F (3) and juncin Z (4), were obtained from the gorgonian coral Junceella fragilis. The structures, including the absolute configurations of briaranes 1 and 2, were elucidated by using spectroscopic methods and comparing the spectroscopic and rotation data with those of known related analogues. Briarane 4 decreased the generation of superoxide anions by human neutrophils. The propionate group in 1 is rarely found.


Assuntos
Antozoários/química , Diterpenos/química , Proteínas de Plantas/química , Animais , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Análise Espectral
13.
Chem Biodivers ; 16(8): e1900317, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264344

RESUMO

Four new diterpenoids named cuceolatins A-D, including three labdane-type (1-3) and one abietane-type (4) as well as three known labdane analogs (5-7), were reported from the leaves of Cunninghamia lanceolata. Structural assignments for these compounds were conducted by analyses of spectroscopic data, and their absolute configurations were determined by time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculations. Among them, the abietane-type diterpenoid (11-hydroxy-12-methoxyabieta-8,11,13-trien-3-one (4)) showed significant cytotoxicity against human MDA-MB-231, MCF-7, and HeLa tumor cell lines with IC50 measurements of 4.3, 2.8 and 4.5 µm, respectively, while the labdane-type diterpenoids with a 4α-carboxy group (1-3 and 5) exhibited moderate antibacterial activity towards Bacillus subtilis and Staphylococcus aureus with IC50 values all below 25 µm.


Assuntos
Cunninghamia/química , Diterpenos/química , /química , /farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Cunninghamia/metabolismo , Teoria da Densidade Funcional , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Conformação Molecular , Folhas de Planta/química , Folhas de Planta/metabolismo , Staphylococcus aureus/efeitos dos fármacos
14.
Mar Drugs ; 17(7)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31336764

RESUMO

The combination of liquid chromatography coupled to high resolution mass spectrometry (LC-HRESMS)-based dereplication and antiproliferative activity-guided fractionation was applied on the Red Sea-derived soft coral Sarcophyton sp. This approach facilitated the isolation of five new cembrane-type diterpenoids (1-5), along with two known analogs (6 and 7), as well as the identification of 19 further, known compounds. The chemical structures of the new compounds were elucidated while using comprehensive spectroscopic analyses, including one-dimensional (1D) and two-dimensional (2D) NMR and HRMS. All of the isolated cembranoids (1-7) showed moderate in vitro antiproliferative activity against a human breast cancer cell line (MCF-7), with IC50 ranging from 22.39-27.12 µg/mL. This class of compounds could thus serve as scaffold for the future design of anticancer leads.


Assuntos
Antozoários/química , Antineoplásicos/farmacologia , Diterpenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Oceano Índico , Concentração Inibidora 50 , Células MCF-7 , Estrutura Molecular
15.
Fitoterapia ; 137: 104259, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319108

RESUMO

The cyclooxygenase-2 (COX-2) is a key enzyme in the synthesis of prostaglandins, its inhibitors are effective for the treatment of inflammation. In this study, an analytical method based on bio-affinity ultrafiltration coupled with ultra performance liquid chromatography and quadrupole-time-of-flight mass spectrometry (BAUF-UPLC-Q-TOF-MS) was established for rapidly screening and identifying COX-2 ligands. Meanwhile, the specificity of the method was verified by denatured COX-2 and inactive compound. Next, the biological activity of ligands screened was proved by enzyme inhibition assay. The preferred binding modes for these COX-2 inhibitors were then determined by molecular docking. Finally, network pharmacology was used to explore the pathways involved anti-inflammatory effects. As a result, five COX-2 inhibitors were selected in the extract of Andrographis Herba (AH), including andrographolide (1), 14-deoxy-11,12-didehydroandrographiside (2), andrographidine E (3), andrographidine D (4), and deoxyandrographolide (5). Among them, compounds 2, 3, 4 and 5 were reported to have COX-2 inhibitory activity for the first time. The result of COX-2 inhibition assay showed that compound 3 had an IC50 of 19 µM, compounds 2 and 5 had an IC50 of >200 µM. And each ligand could bind to multiple amino acid residues of COX-2 based on molecular docking. At last, combined with network pharmacology, these ligands could exert anti-inflammatory effects through three pathways related to COX-2, arachidonic acid metabolism, synthesis of prostaglandins, and prostanoid ligand receptors. The method established in the study could be used to rapidly screen other enzyme inhibitors in complex mixtures, and help to understand the mechanism of action.


Assuntos
Andrographis/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Diterpenos/farmacologia , Cromatografia Líquida de Alta Pressão , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Diterpenos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Humanos , Inflamação , Espectrometria de Massas , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Ultrafiltração
16.
Fitoterapia ; 137: 104263, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295512

RESUMO

Chemical examination of the gum-resin of Boswellia carterii resulted in the isolation and characterization of eighteen new cembrane-type diterpenoids, named as Boscartins P-AG (1-18) and eight known ones. Their structures were established on the basis of extensive spectroscopic (2D NMR, IR, CD, MS and X-ray) analysis in combination with modified Mosher's method. All compounds featured unusual 1,12-oxygenated tetrahydrofuran functionalities, and were evaluated for hepatoprotective activity against D-galactosamine-induced HL-7702 cell damage and cytotoxic activity against MCF-7 human breast cancer cell in vitro. Compounds 1, 6-10, 12-13, 16-17 and 21-25 (10 µM) showed some hepatoprotective activity against D-galactosamine-induced HL-7702 cell damage.


Assuntos
Boswellia/química , Diterpenos/farmacologia , Resinas Vegetais/química , Linhagem Celular , China , Diterpenos/isolamento & purificação , Humanos , Células MCF-7 , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
17.
Fitoterapia ; 137: 104265, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302252

RESUMO

The aromatic plants of Vitex negundo var. heterophylla are not only herb medicine but also a functional food and an industrial crop. Its leaves can be used as a functional food for improving human's health, but the previous studies mainly focused on the volatile constituents, lignans, and iridoids. Our research led to the isolation of four new terpenoids (1-4), together with fifteen known compounds including seven flavonoids (9-15), two jasmonates (7-8) and six terpenoids (5-6, 16-19) from the leaves. Among all these compounds, 1, 2, 11, and 19 exhibited strong inhibitory activity against NO production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage. The anti-inflammatory mechanism of the most active compound (2) is related to the inhibition of iNOS and COX-2, and the suppression of NF-κB pathway. Therefore, terpenoids and flavonoids from the leaves of Vitex negundo var. heterophylla might be used as potential anti-inflammatory candidates for developing medicine or value-added functional food.


Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Norisoprenoides/farmacologia , Vitex/química , Animais , Anti-Inflamatórios/isolamento & purificação , China , Ciclo-Oxigenase 2/metabolismo , Diterpenos/isolamento & purificação , Interleucinas/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Norisoprenoides/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Células RAW 264.7
18.
Fitoterapia ; 136: 104183, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31150767

RESUMO

Diterpenoids are the main secondary metabolites of plants and with a range of biological activities. In the present study, 7 compounds were isolated from the hulls of rice (Oryza sativa L.). Among them, 3 diterpenoids are new namely, 3,20-epoxy-3α-hydroxy- 8,11,13-abietatrie-7-one (1), 4,6-epoxy-3ß-hydroxy-9ß-pimara-7,15-diene (2) and 2-((E)-3- (4-hydroxy-3-methoxyphenyl) allylidene) momilactone A (3). While, 4 terpenoids are known, namely momilactone A (4), momilactone B (5), ent-7-oxo-kaur-15-en-18-oic acid (6) and orizaterpenoid (7). The structures of these diterpenoids were elucidated using 1D and 2D NMR in combination with ESI-MS and HR-EI-MS. Furthermore, all isolated compounds displayed antifungal activities against four crop pathogenic fungi Magnaporthe grisea, Rhizoctonia solani, Blumeria graminearum and Fusarium oxysporum, and phytotoxicity against paddy weed Echinochloa crusgalli. The results suggested that rice could produce plenty of secondary metabolites to defense against weeds and pathogens.


Assuntos
Diterpenos/farmacologia , Fungicidas Industriais/farmacologia , Herbicidas/farmacologia , Oryza/química , Sementes/química , Diterpenos/isolamento & purificação , Echinochloa/efeitos dos fármacos , Fungicidas Industriais/isolamento & purificação , Herbicidas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
19.
Eur J Med Chem ; 176: 513-533, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31151068

RESUMO

From times immemorial, natural products have played an important role in the management of human health. Andrographis paniculata, belonging to the family Acanthaceae and its constituents are reported to possess a wide range of biological properties such as anti-cancer, anti-diabetic, anti-inflammatory, anti-bacterial, anti-malarial, anti-hepatitis, anti-HIV, anti-atherosclerosis, hepatoprotective, FXR antagonist, and α-glucosidase inhibition. Andrographolide (1), is identified as the major bioactive constituent of the plant. Promising biological properties of the major constituent Andrographolide (1) along with structural amenability for facile semi-synthetic modifications have led to the generation of structurally diverse bioactive labdane diterpenes by several research groups. The promising biological activities exhibited by these semi-synthetic derivatives have further kindled interest and the continued research is evidenced through publications, patents and could possibly lead to the development of Andrographolide based medicines in future. The present review aims at compiling and discussing various semi-synthetic derivatives of Andrographolide in relation to their biological properties and their mechanisms of action.


Assuntos
Diterpenos/farmacologia , Andrographis/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/síntese química , Diterpenos/isolamento & purificação , Diterpenos/farmacocinética , Humanos
20.
Phytochemistry ; 165: 112048, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31229789

RESUMO

For the first time, the pigment composition of basidiocarps from the Chilean mushroom Cortinarius pyromyxa was studied under various aspects like phylogeny, chemistry and antibiotic activity. A molecular biological study supports the monotypic position of C. pyromyxa in subgenus Myxacium, genus Cortinarius. Four undescribed diterpenoids, named pyromyxones A-D, were isolated from fruiting bodies of C. pyromyxa. Their chemical structures were elucidated based on comprehensive one- and two-dimensional NMR spectroscopic analysis, ESI-HRMS measurements, as well as X-ray crystallography. In addition, the absolute configurations of pyromyxones A-D were established with the aid of JH,H, NOESY spectra and quantum chemical CD calculation. The pyromyxones A-D possess the undescribed nor-guanacastane skeleton. Tested pyromyxones A, B, and D exhibit only weak activity against gram-positive Bacillus subtilis and gram-negative Aliivibrio fischeri as well as the phytopathogenic fungi Botrytis cinerea, Septoria tritici and Phytophthora infestans.


Assuntos
Antibacterianos/farmacologia , Cortinarius/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Pigmentos Biológicos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Cristalografia por Raios X , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Filogenia , Pigmentos Biológicos/química , Pigmentos Biológicos/isolamento & purificação , Teoria Quântica
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