RESUMO
Leading by the antiviral activities against HSV-2 virus, bioactivity-guided the fraction of crude alkaloids from seeds of Peganum harmala led to the isolation of nine structurally novel indole alkaloids, pegaharolines A - I (1-9), and 11 known ones (10-20). Compound 3 was an unusual 6/5/5/5 spirotetracyclic indole-derived alkaloids featuring a classic bicyclic indole unit fused with an additional pyrrolizine ring via a spiral atom (C-3). Compound 4 was determined as a novel indole alkaloid, characterized with a rare hexacyclic 6/5/6/5-6/6 ring system, by a single-crystal X-ray diffraction. Compounds 5 and 6 were peculiar indole dimers featuring with the rare carbon skeleton of an octacyclic scaffold. Compounds 1-6 were six racemates. Most compounds exhibited different levels of antiviral activities against HSV-2. Especially, the anti-HSV-2 activity of compound 1 (IC50 = 0.90 ± 0.10 µM) was much better than that of the positive control (acyclovir, IC50 = 1.12 ± 0.15 µM). In this study, the discovery of anti-HSV-2 components from the seeds of P. harmala, could benefit development and utilization of this plant in antiviral medicinal products.
RESUMO
Fifteen undescribed lindenane-type sesquiterpenoid dimers, designated chloranholides F-T (1-15), together with twenty-five known analogs (16-40), were isolated from the whole plants of Chloranthus holostegius. The isolate structures were elucidated by analysis of spectroscopic data and chemical methods, and their absolute configurations were determined by X-ray crystallography and electronic circular dichroism spectra. In anti-neuroinflammatory assays, all isolates were evaluated by examination of their inhibitory effect on nitric oxide (NO) in LPS-stimulated BV-2 cells, and the results showed that 21-24, 26, 30, 32 and 36 significantly inhibited the production of the inflammatory mediator NO, with IC50 values ranging from 3.18 to 11.46 µM, which was better than that of quercetin. Structure-activity relationship analysis revealed that two essential functional groups played an indispensable role in the anti-inflammatory effects. Moreover, 22 and 24 inhibited the LPS-induced upregulation of iNOS and COX-2 enzymes in BV-2 microglia at the protein level.
Assuntos
Magnoliopsida , Sesquiterpenos , Microglia/metabolismo , Lipopolissacarídeos/farmacologia , Magnoliopsida/química , Relação Estrutura-Atividade , Sesquiterpenos/química , Óxido Nítrico , Estrutura MolecularRESUMO
One new alkaloid, 6, 7-dimethoxyisoquinoline-N-oxide (1), one new benzofuran derivative, 3,7-dimethyl-6-acetyl-8-benzofuranol (2) and one new lignan, salsolains A (3), along with seven known compounds (4-10), were isolated from the whole plant of Salsola collina Pall. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1 D and 2 D NMR), and their absolute configurations were determined by the X-ray crystallography and ECD calculation. The activities of compounds 1-10 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, especially, compound 5 (50 µM) exhibited the most significant anti-inflammatory activity with the secretion levels of IL-6 and TNF-α at 3.87% and 4.03%, respectively.
Assuntos
Alcaloides , Salsola , Animais , Camundongos , Salsola/química , Fator de Necrose Tumoral alfa , Interleucina-6 , Macrófagos , Células RAW 264.7 , Estrutura MolecularRESUMO
Two new clerodane diterpenoids (1 and 2), a new pyran-2-one derivative (3), along with five known compounds (4â8), were isolated from Croton crassifolius. Notably, crassifolin X (1) is a novel clerodane diterpenoid, characterized with a peculiar δ-lactone core being formed between C-1 and C-4. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (UV, IR, HRESIMS and NMR), and circular dichroism experiments. In addition, all compounds were evaluated for their anti-neuroinflammatory activities based on the expression of TNF-α and IL-6 levels on LPS-induced BV2 cells, and compounds 1â3 and 5 showed potential anti-neuroinflammatory activity.
Assuntos
Croton , Diterpenos Clerodânicos , Diterpenos , Croton/química , Diterpenos/química , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Estrutura Molecular , Raízes de Plantas/química , Piranos/análiseRESUMO
Three new sesquiterpene lactones, named scabertopinolides H - J (1 - 3), along with four known ones, desacylisodeoxyelephantopin 2-methylbutyrate (4), iso-17,19-dihydrodeoxyelephantopin (5), scabertopinolide D (6) and (2R,6R,7R,8S)-8-tigloyloxy-1(10),4(5),11(13)-germacratrien-2,15,6,12-diolide (7) were isolated from the whole plants of Elephantopus scaber. Their structures were elucidated by extensive analysis of spectroscopic data (including IR, UV, HRESIMS, 1 D and 2 D NMR) and single-crystal X-ray. These isolated compounds showed effective anti-inflammatory effects on LPS-stimulated RAW 264.7 cells with IC50 values of 6.27 ± 0.18 to 18.31 ± 1.38 µM.
Assuntos
Asteraceae , Sesquiterpenos , Animais , Asteraceae/química , Lactonas/química , Lactonas/farmacologia , Camundongos , Estrutura Molecular , Compostos Fitoquímicos , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
A phytochemical investigation on the alkaloids from water-soluble part of Sophora alopecuroides led to obtain forty matrine-type alkaloids (1-40) including eighteen new ones (1-18), which covers almost all positions of the oxygen substitution in matrine-type structure. Notably, eight compounds (1-8) belong to rare bis-amide matrine-type alkaloid. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and six instances, verified by X-ray crystallography. Most of isolates showed anti-neuroinflammatory activities based on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BV2 microglia cells. Especially, compound 39 can suppress those two mediator secretions in a dose-dependent manner with IC50 values of 21.6 ± 0.5 and 16.7 ± 0.8 µM, respectively. Further mechanistic study revealed that 39 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF-κB signaling pathway.
Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Quinolizinas/farmacologia , Sophora/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Camundongos , Modelos Moleculares , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Quinolizinas/química , Quinolizinas/isolamento & purificação , Sementes/química , Transdução de Sinais/efeitos dos fármacos , Solubilidade , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Água/química , MatrinasRESUMO
Eight new stilbene dimer xylosides (1-8) and one new flavanol (9), along with seven known ones (10-16) were isolated from the roots of Lysidice rhodostegia. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1D and 2D NMR), ECD calculations and acid hydrolysis. Compounds 1-16 were evaluated for their antioxidant activities using DPPH radical-scavenging assay. Especially, compounds 9 and 10 exhibited stronger antioxidant effects than the positive control (vitamin E), with IC50 values of 9.57 ± 1.30 and 13.60 ± 1.47 µM, respectively.
Assuntos
Antioxidantes/farmacologia , Fabaceae/química , Glicosídeos/farmacologia , Polifenóis/farmacologia , Estilbenos/farmacologia , Antioxidantes/isolamento & purificação , China , Glicosídeos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Polifenóis/isolamento & purificação , Estilbenos/isolamento & purificaçãoRESUMO
Five matrine-type alkaloids (1â5) including two new compounds (1 and 3) and a new natural product (2) were isolated from the roots of Sophora tonkinesis. Their structures were identified by extensive spectroscopic analysis (UV, IR, HRESIMS and NMR). The absolute configurations of 2 and 3 were determined by X-ray diffraction. Compounds 1â5 were evaluated their activity against inflammatory cytokines TNF-α and IL-6 levels on LPS-induced RAW 264.7 macrophages, and compound 1 showed the most significant activity, potent than that of matrine, the representative ingredient from Sophora plants.
Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/química , Quinolizinas/farmacologia , Sophora/química , Alcaloides/química , Animais , China , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Raízes de Plantas/química , Células RAW 264.7 , MatrinasRESUMO
A new sesquiterpene pyridine alkaloid (1), along with four known compounds (2-5), were isolated from the stems and leaves of Euonymus fortunei. The new structure was determined by extensive spectroscopic analyses (IR, UV, NMR, HRESIMS and ECD). In addition, compound 3 showed a stronger anti-respiratory syncytial virus (RSV) activity with an IC50 value of 1.20 ± 0.10 µM than the positive control ribavirin with an IC50 value of 5.62 ± 0.49 µM.[Formula: see text].
Assuntos
Alcaloides , Euonymus , Sesquiterpenos , Estrutura Molecular , Folhas de Planta , PiridinasRESUMO
Two new isoquinoline alkaloids, 6 R,6aS-N-nantenine Nß-oxide (1), 6S,6aS-N-nantenine Nα-oxide (2), along with nine known alkaloids, nantenine (3), oxonantenine (4), protopine (5), nornantenine (6), N-methyl-laurotetanine (7), isocorydine (8), O-methyflavinantine (9), N-methyl-2,3,6-trimethoxymorphinan-dien-7-one Nß-oxide (10) and (+)-10-O-methylhernovine Nß-oxide (11) were isolated from the seeds of Nandina domestica. Their structures were elucidated by extensive analyses of spectroscopic data (IR, UV, HRESIMS, 1 D and 2 D NMR), ECD calculation and comparison with the related literatures. In addition, the cytotoxicity against A549 cells of these alkaloids was determined by the MTT assay.
Assuntos
Alcaloides , Berberidaceae , Isoquinolinas/farmacologia , Células A549 , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Berberidaceae/química , Humanos , Isoquinolinas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais , Sementes/químicaRESUMO
Pegaharines A-G (1-6), six novel ß-carboline alkaloids representing three types of skeleton, were isolated from the seeds of Peganum harmala. Compound 1 is a peculiar ß-carboline alkaloid characterized by the unprecedented carbon skeleton of an azepine-indole system. Compounds 3-6 represent the first examples of heterodimers constructed from rare tetracyclic ß-carboline and classic tricyclic ß-carboline alkaloids. Compounds 1 and 2 were characterized by X-ray crystallography. Compound 4 exhibited strong antiviral activity against HSV-2, with an IC50 value of 2.12 ± 0.14 µM.
Assuntos
Alcaloides/química , Antivirais/farmacologia , Carbolinas/química , Herpesvirus Humano 2/efeitos dos fármacos , Peganum/química , Extratos Vegetais/química , Antivirais/química , Herpesvirus Humano 2/química , Estrutura Molecular , Sementes/químicaRESUMO
Six new compounds, hyperpatulones A-F (1-6), along with ten additional known related derivatives (7-16), were isolated from Hypericum patulum (Guttiferae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR), X-ray crystallography, electronic circular dichroism (ECD) spectroscopy and Rh2(OCOCF3)4-induced ECD. All compounds were tested for their cytotoxic activities on human HepG-2, HeLa, MCF-7, and A549 cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compound 5 exhibited significant cytotoxicities against HepG-2, HeLa and A549 cell lines with IC50 values of 9.52 ± 0.27, 11.87 ± 0.22 and 12.63 ± 0.12 µM, respectively.
RESUMO
Three new prenylated acetophenone derivatives, acronyculatin P (1), acronyculatin Q (2), and acronyculatin R (3) were isolated from the leaves of Acronychia oligophlebia. Their structures were identified by extensive analyses of spectroscopic data (IR, UV, ESI-HRMS, 1D and 2D NMR) and comparison with the literatures. In addition, the cytotoxic activity against MCF-7 cells of the compounds were evaluated by the MTT assay and the IC50 values were 56.8, 40.4 and 69.1 µM, respectively.
Assuntos
Acetofenonas/isolamento & purificação , Rutaceae/química , Acetofenonas/química , Acetofenonas/farmacologia , Humanos , Células MCF-7 , Folhas de Planta/química , PrenilaçãoRESUMO
Five novel quinolizidine-based alkaloids (1-5) were obtained from the seeds of Sophora alopecuroides L. Compounds 1 and 2 are the first examples of sparteine-indolizine and matrine-indolizine alkaloids, respectively, whereas 3 and 4 are epimeric normatrine-julolidine alkaloids with unusual skeletons. The structures of these compounds were determined by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Hypothetical biosynthetic pathways of 1-5 were proposed. Compound 2 exhibited significant antiviral activity against the hepatitis B virus.
RESUMO
Seven undescribed phloroglucinol derivatives, tomentodiones N-T, and eleven known ones were isolated from Rhodomyrtus tomentosa. Tomentodione N is the first example of a ß-triketone unit coupled with an isoamyl alcohol through a furan fused-ring, and tomentodiones N, S, T were three racemates. The undescribed structures were elucidated by means of spectroscopic, X-ray diffraction, electronic circular dichroism calculation, and chemical methods. In addition, the isolated compounds were determined for the cytotoxic activities on HeLa cells and anti-inflammatory activities in LPS-stimulated RAW 264.7â¯cells.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Myrtaceae/química , Floroglucinol/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Floroglucinol/análogos & derivados , Floroglucinol/química , Células RAW 264.7 , Relação Estrutura-Atividade , Células VeroRESUMO
Seven sesquiterpene lactones, 8-O-methacryloylelephanpane, 2,4-bis-O-methyl-8-O-methacryloylelephanpane, 4-O-ethyl-8-O-methacryloylelephanpane, 8-O-methacryloylisoelephanpane, 2-O-demethyltomenphantopin C, molephantin A, molephantin B, along with ten known ones, were isolated from Elephantopus mollis (Asteraceae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolates were evaluated for their anti-inflammatory activities on LPS-stimulated RAW 264.7 cells, and all tested compounds exhibited potent anti-inflammatory effects with IC50 values of 0.57 ± 0.17 to 14.34 ± 1.61 µM, except that compound tomenphantopin C exhibited moderate anti-inflammatory activity with IC50 values of 59.97 ± 1.53 µM.
Assuntos
Anti-Inflamatórios/química , Asteraceae/química , Sesquiterpenos/química , Animais , Anti-Inflamatórios/isolamento & purificação , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Células RAW 264.7 , Sesquiterpenos/isolamento & purificaçãoRESUMO
Four novel matrine-based alkaloids (1-4) were isolated from the seeds of Sophora alopecuroides. Compounds 1 and 2 possess unprecedented 6/6/6/4 and 6/5/6/6 ring systems, respectively, while 3 and 4 are a pair of stereoisomeric matrine-acetophenone alkaloids with an unusual skeleton. Their structures were elucidated by means of spectroscopic methods and single-crystal X-ray diffraction. Hypothetical biogenetic pathways for 1-4 are proposed, and their antiviral activities are also discussed.
Assuntos
Alcaloides/química , Quinolizinas/química , Antivirais , Vírus da Hepatite B , Estrutura Molecular , Sementes , Sophora , MatrinasRESUMO
Five new diterpenoid alkaloids, ajacisines A-E (1-5), were isolated from Delphinium ajacis, along with seven known alkaloids (6-12). On the basis of their spectral data (IR, UV, HR-ESI-MS, 1D and 2D NMR) and chemical properties, the structures of compounds 1-12 were identified. All isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus, and compounds 3-5 and 8 exhibited moderate to weak effects with IC50 values of 75.2 ± 1.1, 35.1 ± 0.6, 10.1 ± 0.3, and 50.2 ± 0.5 µM, respectively.
Assuntos
Alcaloides/farmacologia , Antivirais/farmacologia , Delphinium/química , Diterpenos/farmacologia , Estrutura Molecular , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Alcaloides/química , Alcaloides/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Raízes de Plantas/química , Caules de Planta/químicaRESUMO
Olfaction is primarily mediated by highly specified olfactory receptors (ORs). Here, we cloned and identified an olfactory receptor, named SlituOR1 (Genbank no. JN835269), from Spodoptera litura and found evidence that it is a candidate pheromone receptor. It exhibited male-biased expression in the antennae, where it was localized at the base of sensilla trichoidea, the antennal sensilla mainly responsive to pheromones in moths. Conserved orthologues of this receptor, found among known pheromone receptors within the Lepidoptera, and SlituOR1 were placed among a clade of candidate pheromone receptors in a phylogeny tree of insect OR gene sequences. SlituOR1 showed differential expression in S. litura populations attracted to traps baited with different ratios of the two sex pheromone components (9Z,11E)-tetradecadienyl acetate (Z9E11-14:OAc) and (9Z,12E)-tetradecadienyl acetate (Z9E12-14:OAc). Knocking down of SlituOR1 by RNA interference reduced the electroantennogram (EAG) response to Z9E11-14:OAc, and this result is consistent with the field trapping experiment. We infer that variation in transcription levels of olfactory receptors may modulate sex pheromone perception in male moths and could provide some of the flexibility required to maintain the functionality of communication with females when a population is adapting to a new niche and reproductive isolation becomes an advantage.
Assuntos
Sensilas/metabolismo , Atrativos Sexuais/farmacologia , Spodoptera/genética , Spodoptera/fisiologia , Animais , Antenas de Artrópodes/efeitos dos fármacos , Antenas de Artrópodes/metabolismo , Fenômenos Eletrofisiológicos , Feminino , Perfilação da Expressão Gênica , Proteínas de Insetos/genética , Masculino , Filogenia , Interferência de RNA , Receptores de Feromônios/genética , Sensilas/efeitos dos fármacos , Análise de Sequência de DNA , Atrativos Sexuais/químicaRESUMO
Three new diterpenoids, including one labdane diterpenoid (1) and two cembrane diterpenoids (2-3), were isolated from the aerial parts of Croton laui, along with four known analogues (4-7). Their structures were elucidated by spectroscopic analysis and comparison with literature data. All compounds were evaluated for their cytotoxicity against two tumour cell lines.