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1.
Bioorg Chem ; 116: 105332, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34509045

RESUMO

Sixteen chebulic acid derivatives, including nine new (1-9) and seven known (10-16) ones, were isolated from an ethanol extract of the branches and leaves of Balakata baccata. The structures of the new compounds were elucidated by their UV, IR, HRESIMS, NMR, electronic circular dichroism (ECD) and single-crystal X-ray diffraction data. The effects of all the isolates on antineuroinflammatory and antioxidant activities were evaluated. Compared with the positive control minocycline (IC50 = 1.21 ± 0.71 µM), compounds 1-16 with IC50 values being greater than 50 µM, displayed almost no effects on the inhibition of NO production in LPS-induced BV-2 microglial cells, however, the results of antioxidant activity for compounds 1-16 showed significant DPPH-radical scavenging abilities with EC50 value ranging from 3.98 to 14.24 µM, while the EC50 value of positive control vitamin C was 14.31 µM. At last, the results of PCR (qRT-PCR) analysis showed that compound 1 could enhance the expression of antioxidases (HO-1, GCLC, and NQO1) at the mRNA levels.

2.
Chem Biodivers ; 18(11): e2100272, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34532975

RESUMO

The aim of the present work is to isolate a series of triterpene derivatives with rhamnosyl linking acetyl groups from Glechoma longituba according to the structural characteristics of previously described triterpene saponins. The extract ion chromatography spectrum of the crude extract of G. longituba was detected and analyzed by HPLC-HR-ESI-MS to determine possible components, and these metabolites were traced and separated by combining high-resolution mass spectrometry and predicted liquid chromatography retention time. Three 11α, 12α-epoxypentacyclic oleanolic acid triterpene saponins (glechomanosides H-J) and one ursane triterpene aldehyde saponin with a C-28 aldehyde group were isolated from G. longituba. The structure of these compounds was confirmed by NMR and compared with those of previously characterized compounds. The strategy described in this report enables a rapid, reliable, and complete analysis of glycoside compounds containing different numbers of acetyl groups at different positions on the sugar.

3.
Fitoterapia ; 153: 104990, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34246746

RESUMO

Three novel lignans (1, 5 and 6) and two novel quinic acids (16 and 17) along with 15 known phenylpropanoids were obtained from the ethanol extract of Zanthoxylum nitidum var. tomentosum (Rutaceae). Their structures were confirmed by comprehensive spectroscopic data (NMR and HRESIMS), and the absolute configurations of all novel compounds were elucidated based on electronic circular dichroism (ECD) spectroscopic data. The production of nitric oxide (NO) in BV-2 microglial cells induced through lipopolysaccharide (LPS) was used to evaluate in vitro anti-neuroinflammatory activity of compounds 1-20. Compound 2, 3, 7 and 16 showed excellent inhibition of LPS-induced NO production. The structure-activity relationships of the isolates were investigated. In addition, the mechanism of action of 2 was elucidated by RT-PCR and Western blotting analysis, which indicated that it reduced neuroinflammatory mainly through NLRP3/caspase1 signaling pathways in LPS-induced BV2 microglial cells.


Assuntos
Anti-Inflamatórios/farmacologia , Lignanas/farmacologia , Microglia/efeitos dos fármacos , Zanthoxylum/química , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , China , Lignanas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Transdução de Sinais/efeitos dos fármacos
4.
J Nat Prod ; 84(4): 1316-1325, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33822610

RESUMO

Three new tyramine-type alkamides (1-3), three new natural products (4-6), five new N-acylated/formylated aporphine alkamides with different ratios of rotational isomers (7-11), and 20 known alkamides (12-31) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of compounds 7, 8, and 10 were determined by single-crystal X-ray diffraction analysis. In the biological activity assay, compounds 3, 5, and 10-23 displayed inhibitory effects against lipopolysaccharide-induced NO release in BV-2 microglial cells, exhibiting IC50 values of 0.93-45 µM.

5.
Fitoterapia ; 151: 104877, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33667564

RESUMO

Five new flavonol glycosides (1-5), one new phenylpropanoid glycoside (6), and nine known glycosides (7-15) were isolated from the stems and leaves of Neoshirakia japonica. The structures of the new compounds were determined by detailed analysis of spectroscopic data (HRESIMS, 1D and 2D NMR) and acid hydrolysis experiment. The antineuroinflammatory effects of all the isolates were evaluated by inhibiting NO production against LPS-induced BV-2 microglial cells. Compounds 1, 8, and 9 showed more potent inhibitory activities with IC50 values of 2.7, 5.5, and 4.1 µM, respectively, than that of the positive control minocycline (IC50 = 15.6 µM), while compounds 7 (IC50 = 17.0 µM) and 10 (IC50 = 24.3 µM) also displayed inhibitory activities to a certain degree.


Assuntos
Anti-Inflamatórios/farmacologia , Euphorbiaceae/química , Flavonóis/farmacologia , Glicosídeos/farmacologia , Microglia/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , China , Flavonóis/isolamento & purificação , Glicosídeos/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Caules de Planta/química
6.
J Org Chem ; 86(2): 1462-1470, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33410687

RESUMO

Nitidumpeptins A and B (1 and 2), two novel cyclic hexapeptides, were isolated from the herb Zanthoxylum nitidum var. tomentosum. Their planar structures were elucidated based on NMR and MS spectrometric analysis, and the absolute configurations were determined by the Marfey's method. Structurally, 1 is a unique peptide with a backbone bearing a pyrrolidine-2,5-dione unit, which is the first occurrence moiety specifically in a naturally occurring cyclohexapeptide. The total synthesis of 1 and 2 was achieved by solution-phase in parallel with solid-phase peptide synthesis, and their absolute configurations were further confirmed. The combination of 2 with gefitinib exhibited synergistic antiproliferative activity in acquired gefitinib-resistant non-small cell lung cancer cells (HCC827-gef). The underlying mechanism for the antiproliferative activity of 2 was in part associated with the suppression of YAP expression in HCC827-gef cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Zanthoxylum , Humanos , Pirrolidinas
7.
Eur J Med Chem ; 210: 112951, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33109400

RESUMO

Four series of new 3-nitro naphthalimides derivatives, 4(4a‒4f), 5(5a‒5i), 6(6a‒6e) and 7 (7a‒7j), were designed and synthesized as antitumor agents. Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective in vitro antiproliferative activity on SMMC-7721, T24, SKOV-3, A549 and MGC-803 cancer cell lines in comparison with 5-fluorouracil (5-FU), mitonafide and amonafide. Nude mouse xenotransplantation model assay results indicated that compounds 6b and 7b exhibited good in vivo antiproliferative activity in MGC-803 xenografts in comparison with amonafide and cisplatin, suggesting that compounds 6b and 7b could be good candidates for antitumor agents. Gel electrophoresis assay indicated that DNA and Topo I were the potential targets of compounds 6b and 7b, and comet assay confirmed that compounds 6b and 7b could induce DNA damage, while the further study showed that the 6b- and 7b-induced DNA damage was accompanied by the upregulation of p-ATM, P-Chk2, Cdc25A and p-H2AX. Cell cycle arrest studies demonstrated that compounds 6b and 7b arrested the cell cycle at the S phase, accompanied by the upregulation of the expression levels of the antioncogene p21 and the down-regulation of the expression levels of cyclin E. Apoptosis assays indicated that compounds 6b and 7b caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-3, caspase-9 and PARP and the downregulation of Bcl-2. These mechanistic studies suggested that compounds 6b and 7b exerted their antitumor activity by targeting to DNA, thereby inducing DNA damage and Topo I inhibition, and consequently causing S stage arrest and the induction of apoptosis.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Naftalimidas/química , Naftalimidas/farmacologia , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Humanos , Camundongos Nus , Naftalimidas/síntese química , Neoplasias/tratamento farmacológico , Neoplasias/genética
8.
Bioorg Chem ; 105: 104332, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33038553

RESUMO

Four new diterpenoids (1-4), three new triterpenoids (12-14), and seven known diterpenoids (5-11) were obtained from an aqueous EtOH extract of the aerial parts of Triadica rotundifolia. The structures of new compounds were determined by spectroscopic techniques. Their absolute configurations were verified via single-crystal X-ray diffraction data, Mo2(OAc)4 induced electronic circular dichroism (ECD), and ECD calculations. The antineuroinflammatory effects of the isolates were assessed by inhibiting NO production in LPS-induced BV-2 microglial cells. Compared with the positive control minocycline (IC50 = 16.1 µM), compounds 3, 8, 11 showed moderate inhibitory activities with IC50 values of 35.9, 17.0, 31.5 µM, respectively.


Assuntos
Diterpenos/química , Euphorbiaceae/química , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Triterpenos/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Humanos , Minociclina/farmacologia , Minociclina/uso terapêutico , Modelos Moleculares , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Triterpenos/farmacologia
9.
Fitoterapia ; 146: 104684, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32634455

RESUMO

A decoction of Plumeria rubra flowers has been used traditionally for the treatment of diabetes in China and Mexico. Chemical investigations on the bioactive constituents of these flowers led to the isolation of 30 compounds, including the four new compounds, one iridoiod (1), two triterpenoids (4, 5), and a long-chain δ-lactone (16). In addition, 26 known compounds (2, 3, 6-15, 17-30) are also reported. All of these compounds were identified on the basis of spectroscopic data interpretation and the absolute configurations of compound 4, 5, 16 were determined by Mosher's method. Compounds 1-4, 7, 8 and 16 showed moderate to significant inhibitory activities against α-glucosidase and protein tyrosine phosphatase 1B, with 4 having IC50 values of 19.45 µM and 0.21 µM, respectively.


Assuntos
Apocynaceae/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Lactonas/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Terpenos/farmacologia , China , Flores/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Lactonas/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Terpenos/isolamento & purificação
10.
Nat Prod Res ; : 1-6, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081038

RESUMO

One new long-chain ester derivative of trans-ferulic acid 1 and one natural tirucallane-type triterpenoid 2, together with forty known compounds (3-42), were isolated from the barks of Melia azedarach. Their structures were established on the basis of spectroscopic data interpretation. Compounds 7, 9, 10, 12, 13 showed significant inhibitory activities against PTP1B with IC50 values of 13.82 ± 1.29 µM, 13.29 ± 2.26 µM, 20.27 ± 0.52 µM, 24.36 ± 1.25 µM, 15.23 ± 0.6 µM, respectively.

11.
Fitoterapia ; 142: 104486, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31987982

RESUMO

Inflammation is a very common and important basic pathological process. There is still a great need for the isolation of effective anti-inflammatory agents from plants. In this paper, five new isobutylamides, zanthoxylumamides E-I (1-5), and four known isobutylamides (6-9) were isolated from Zanthoxylum nitidum var. tomentosum (Rutaceae). Chiral resolution of seven racemic isobutylamides (1-4 and 6-8) was successfully performed, and the absolute configurations of two stereoisomers of 1-4 were validated by ECD and NMR. The obtained isobutylamides were evaluated in vitro anti-inflammatory activity with the lipopolysaccharide (LPS)-stimulated production of nitric oxide (NO) in murine macrophage RAW264.7 cells. Compound 8 exhibited significant inhibition of LPS-induced NO production. The underlying molecular mechanisms of the anti-inflammatory activity of 8 revealed that it suppressed the NO production through the modulation of myeloid differentiation factor 88 (MyD88) and interferon regulatory factor 3 (IRF3) signaling pathways.


Assuntos
Amidas/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Zanthoxylum/química , Amidas/química , Animais , Sobrevivência Celular , Lipopolissacarídeos/toxicidade , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7
12.
J Biol Chem ; 294(51): 19589-19603, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31727741

RESUMO

Although the extracellular ATP-gated cation channel purinergic receptor P2X5 is widely expressed in heart, skeletal muscle, and immune and nervous systems in mammals, little is known about its functions and channel-gating activities. This lack of knowledge is due to P2X5's weak ATP responses in several mammalian species, such as humans, rats, and mice. WT human P2X5 (hP2X5Δ328-349) does not respond to ATP, whereas a full-length variant, hP2X5 (hP2X5-FL), containing exon 10 encoding the second hP2X5 transmembrane domain (TM2), does. However, although rat P2X5 (rP2X5) has a full-length TM2, ATP induces only weak currents in rP2X5, which prompted us to investigate the mechanism underlying this small ATP response. Here, we show that single replacements of specific rP2X5 residues with the corresponding residues in hP2X5 (S191F or F195H) significantly enhance the current amplitude of rP2X5. Using a combination of engineered disulfide cross-linking, single-channel recording, and molecular modeling, we interrogated the effects of S191F and F195H substitutions on the allostery of the left flipper (LF) domain. On the basis of our findings, we propose that the bound ATP-induced distinct allostery of the LF domain with that of other functional subtypes has caused the weak ATP response of rP2X5 receptors. The findings of our study provide the prerequisite for future transgenic studies on the physiological and pathological functions of P2X5 receptors.


Assuntos
Trifosfato de Adenosina/química , Receptores Purinérgicos P2X5/química , Sítio Alostérico , Animais , Biotinilação , Cátions , Reagentes para Ligações Cruzadas , Dissulfetos/química , Éxons , Células HEK293 , Humanos , Simulação de Dinâmica Molecular , Domínios Proteicos , Ratos , Proteínas Recombinantes de Fusão/química
13.
J Nat Prod ; 82(11): 3056-3064, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31668072

RESUMO

Three new germacrane sesquiterpenoid-type alkaloids with an unusual Δ8-7,12-lactam moiety, glechomanamides A-C (1-3), and two pairs of 7,12-hemiketal sesquiterpenoid epimers (4a/b, 5a/b) were isolated from Salvia scapiformis. Their structures were elucidated by spectroscopic methods including HRESIMS, IR, UV, and 1D and 2D NMR and also confirmed by single-crystal X-ray diffraction analysis. The chemical transformation of compounds 1-5 in a solution environment was analyzed by 2D NMR spectroscopy. The aza acetallactams (1-3) were stable in organic solvent, while single crystals of the hemiacetal esters (4a/b, 5a/b) underwent a tautomeric equilibrium after being dissolved. Single crystals of 4a, 4b, and 5a were obtained for the first time as their naturally occurring forms. Glechomanamide B (2) exhibited antiangiogenic activity by suppression of vascular endothelial growth factor (VEGF)-induced tube formation through modulation of VEGF receptor 2 (VEGFR2)-mediated signaling pathways in human umbilical vascular endothelial cells (HUVECs). In addition, compound 2 also showed the significant suppression of mRNA expression associated with glycolysis and angiogenesis biomarkers in high glucose (30 mM)-induced HUVECs. These findings suggest that compound 2 might be a potential lead compound candidate for the management of diabetic retinopathy.


Assuntos
Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Lactamas/química , Lactamas/farmacologia , Salvia/química , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Retinopatia Diabética/tratamento farmacológico , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
14.
Fitoterapia ; 138: 104345, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31470063

RESUMO

The present study reports the phytochemical investigation of n-butanol-soluble extracts of Glechoma longituba. Five new oleanane-type triterpenoid saponins with an 11α, 12α-epoxy unit, named glechomanosides A - E, were isolated from the n-butanol soluble fraction of G. longituba. Their chemical structures were established using HRESIMS, IR, 1D NMR, and 2D NMR techniques. The compounds were all evaluated for their antithrombus activities by monitoring thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antiplatelet aggregation assays. These results suggest that G. longituba might be a candidate plant source of an interesting antithrombotic activity.


Assuntos
Plaquetas/efeitos dos fármacos , Lamiaceae/química , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , China , Feminino , Masculino , Camundongos , Estrutura Molecular , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Tempo de Tromboplastina Parcial , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Agregação Plaquetária , Tempo de Protrombina , Coelhos , Saponinas/isolamento & purificação , Tempo de Trombina
15.
Phytomedicine ; 63: 153037, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357075

RESUMO

BACKGROUND: Non-Small-Cell Lung Cancer (NSCLC) is the most-frequent cause of cancer death, and novel chemotherapeutic drugs for treating NSCLC are urgently needed. 2α, 3α, 23-trihydroxy-13α, 27-cyclours-11-en-28-oic acid (euscaphic acid G) is a new hexacyclic triterpene acid isolated by our group from Glechoma longituba (Nakai) Kupr. However, the underlying mechanisms responsible for the anticancer effects of hexacyclic triterpene acid have not been elucidated. PURPOSE: In the present work, we evaluated growth inhibitory effect of the new isolated hexacyclic triterpene acid and explored the underlying molecular mechanisms. METHODS/STUDY DESIGNS: Herbs were extracted and constituents were purified by chromatographic separation, including silica gel, ODS, MCI, Sephadex LH-20 and preparative HPLC. The compound structures were elucidated by the use of UV, NMR and MS spectral data. The anticancer activity of euscaphic acid G was evaluated by MTT assay. Cell cycle, apoptosis, reactive oxygen species and mitochondrial membrane potential were determined by flow cytometry. To display the possible mechanism of euscaphic acid G on NCI-H460 cells, RT-PCR, immunofluorescence and Western blot analysis were carried out. RESULTS: A new hexacyclic triterpene acid, euscaphic acid G, together with fifteen known triterpenoids, was isolated from the aerial parts of G. longituba. Our results showed that euscaphic acid G exerted strong anti-proliferative activity against NCI-H460 cells in a concentration- and time-dependent manner. Flow cytometry demonstrated euscaphic acid G arrested the cell cycle at G1 phase, induced cellular apoptosis, accompanied by ROS generation and mitochondrial membrane potential reduction. Mechanistic studies revealed that euscaphic acid G treatment inhibited IKKα/ß phosphorylation and IκBα phosphorylation, which subsequently caused the blockage of NF-κB p65 phosphorylation and nuclear translocation. CONCLUSION: In conclusion, these results suggested that euscaphic acid G from G. longituba showed potential anticancer effects against lung cancer cells via inducing cell cycle arrest and apoptosis, at least partly, through NF-κB signaling pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Lamiaceae/química , NF-kappa B/antagonistas & inibidores , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/química
16.
Medchemcomm ; 10(4): 584-597, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31057738

RESUMO

A series of asiatic acid (AA) based 1,2,3-triazole derivatives were designed, synthesized and subjected to a cell-based NF-κB inhibition screening assay. Among the tested compounds, compound 6k displayed impressive NF-κB inhibitory activity with an IC50 value in the low micromolar range. A molecular docking study was performed to reveal key interactions between 6k and NF-κB in which the 1,2,3-triazole moiety and the hydroxyl groups of the AA skeleton were important for improving the inhibitory activity. Subsequently, surface plasmon resonance analysis validated the high affinity between compound 6k and NF-κB protein with an equilibrium dissociation constant (KD) value of 0.36 µM. Further studies showed that compound 6k observably inhibited the NF-κB DNA binding, nuclear translocation and IκBα phosphorylation. Moreover, in vitro antitumor activity screening showed that compound 6k (IC50 = 2.67 ± 0.06 µM) exhibited the best anticancer activity against A549 cells, at least partly, by inhibition of the activity of NF-κB. Additionally, the treatment of A549 cells with compound 6k resulted in apoptosis induction potency and in vitro cell migration inhibition. Thus, we conclude that AA based 1,2,3-triazole derivatives may be potential NF-κB inhibitors with the ability to induce apoptosis and suppress cell migration.

17.
Chem Biodivers ; 16(5): e1900123, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30933425

RESUMO

Two previously undescribed guaiane-type sesquiterpenes (1 and 2), a pair of new salvialane-type sesquiterpenes (3a and 3b), together with 11 known compounds were isolated and purified from the rhizomes of Curcuma kwangsiensis. Their structures were elucidated by the extensive spectroscopic data (1D- and 2D-NMR) analysis. All the isolated compounds were assessed for their anti-neuroinflammatory activity by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine BV-2 microglial cells in vitro assay, and the isolates 3 and 11 showed anti-neuroinflammatory activity with IC50 values of 1.85 and 20.05 µm, respectively.


Assuntos
Anti-Inflamatórios/química , Curcuma/química , Sesquiterpenos/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Linhagem Celular , Curcuma/metabolismo , Lipopolissacarídeos/toxicidade , Espectroscopia de Ressonância Magnética , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Conformação Molecular , Óxido Nítrico/metabolismo , Rizoma/química , Rizoma/metabolismo , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia
18.
J Enzyme Inhib Med Chem ; 34(1): 753-760, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30829084

RESUMO

The aerial parts of Tetrastigma hemsleyanum (APTH) have been used as a functional tea in China. The purpose of the current study was to identify the bioactive constituents with inhibitory activity against soluble epoxide hydrolase (sEH) and inducible nitric oxide synthase (iNOS), which are jointly considered potential therapeutic targets for vascular system diseases. In the present study, 39 compounds (1-39) were isolated from the APTH. Among them, compounds 8, 10, 12, 16, 17, 19, and 32 displayed potential activities, with IC50 values ranging from 4.5 to 9.5 µM, respectively, and all in non-competitive inhibition mode. Compounds 5, 10, 12, 19, and 32 displayed potent iNOS inhibitory effects, with IC50 values ranging from 15.6 to 47.3 µM. The results obtained in this work contribute to a better understanding of the pharmacological activities of T. hemsleyanum and its potential application as a functional food.


Assuntos
Epóxido Hidrolases/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Fenóis/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Vitaceae/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Epóxido Hidrolases/metabolismo , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico Sintase/metabolismo , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Solubilidade , Relação Estrutura-Atividade
19.
J Asian Nat Prod Res ; 21(6): 522-527, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29665732

RESUMO

A new natural product, 3α,19-dihydroxyl-ent-pimara-8(14),15-diene (1), which possesses an α-orientation hydroxymethyl at C-4 and ∆8,14 groups, as well as eight known compounds, was isolated from the rhizomes of Ricinus communis. The structure of 1 was elucidated by extensive spectroscopic methods and its absolute configurations were confirmed by X-ray crystallographic analysis. The inhibitory rate of 1 against protein tyrosine phosphatase 1B (PTP1B) was 49.49% at the concentration of 6.58 × 10-5 mol/L.


Assuntos
Diterpenos/química , Diterpenos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Ricinus/química , Animais , Cristalografia por Raios X , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Camundongos , Conformação Molecular , Estrutura Molecular , Rizoma/química
20.
Fitoterapia ; 130: 281-289, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30240842

RESUMO

Matrix metalloproteinase 9 (MMP-9) is one of the structurally related zinc-dependent endopeptidases families and provides a new target for cancer therapy owing to its pivotal role in metastatic tumors. In this paper, fourteen lignans, including three novel lignans, named selamoellenin B-D (1-3), and eleven known lignan derivatives (4-14) were isolated from the plant of Selaginella moellendorffii. Among them, compound 3 is optically active, which was enantiomerically seperated to afford a pair of enantiomers, (-)-3 and (+)-3. Their structures were elucidated by extensive spectroscopic analyses. Their cytotoxic activities were evaluated against four human cancer cell lines. Among them, five compounds (4, 5, 6, 11 and 13) exhibited great potent cytotoxicity and their structure-activity relationships were also discussed. All compounds except for 3 lignan analogues with low cytotoxicity were selected for further in vitro enzyme inhibition, surface plasmon resonance (SPR), and molecular docking assays based on the MMPs target. The results shown that, compound 11 have the best inhibitory effect and can be considered as a potential drug candidate targeting at MMP-9 for cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Lignanas/farmacologia , Inibidores de Metaloproteinases de Matriz/farmacologia , Selaginellaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Lignanas/isolamento & purificação , Metaloproteinase 9 da Matriz , Inibidores de Metaloproteinases de Matriz/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Relação Estrutura-Atividade
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