RESUMO
Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.
RESUMO
Two new cucurbitane-type triterpenoid saponins, 2,20ß,22ß-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-ß-D-glucopyranoside (1), 2,20ß,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-ß-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 µM against paracetamol-induced HepG2 cell damage.
RESUMO
Three new flavonoids including two isoflavanones sophortones A and B (1 and 2), and one chalcone sophortone C (3) were isolated from the roots of Sophora tonkinensis. Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.
RESUMO
Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 µM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.
Assuntos
Carthamus tinctorius , Glicosídeos , Oxirredução , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Animais , Carthamus tinctorius/química , Ratos , Estrutura Molecular , Neurônios/efeitos dos fármacos , Relação Estrutura-Atividade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Relação Dose-Resposta a Droga , Córtex Cerebral/efeitos dos fármacos , Chalconas/farmacologia , Chalconas/química , Chalconas/isolamento & purificaçãoRESUMO
Six new iridoid glycosides were isolated from the ethyl acetate fraction of the whole plants of Hedyotis diffusa Willd. They were identified as E-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (1), Z-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (2), E-6-O-caffeoyl scandoside methyl ester (3), E-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (4), Z-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (5), and E-6-O-p-coumaroyl-4'-O-acetyl scandoside methyl ester (6). The structures of them were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, and NMR). They were screened for anti-inflammatory effect, antioxidant effect, antitumor effect, and neuroprotective effect and did not show potent activities.
Assuntos
Ácidos Cumáricos , Hedyotis , Glicosídeos Iridoides , Glicosídeos Iridoides/farmacologia , Hedyotis/química , Antioxidantes , Espectroscopia de Ressonância Magnética , Ésteres , Glicosídeos/farmacologiaRESUMO
Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC50 values of 5.69, 6.16, and 6.84 µM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents.
Assuntos
Hedyotis , Iridoides , Iridoides/farmacologia , Iridoides/química , Hedyotis/química , Extratos Vegetais/química , Relação Estrutura-Atividade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/químicaRESUMO
Six undescribed lavandulylated flavonoids (1-6) were isolated from the roots of Sophora flavescens. Remarkably, compounds 1 and 2, which were composed of a flavane unit and a phloroglucinol unit, were the first reported dimers. Compounds 3 and 4 were the first reported neoflavonoids with lavandulyl units. Compounds 5 and 6 were chalcone with oxidized lavandulyl units. Their structures were fully characterized by cumulative analyses of UV, IR, HRESIMS, NMR and ECD spectroscopic data, along with computational calculations through density functional theory. Compounds 1 and 2 showed significant protein tyrosine phosphatase-1B inhibitory activities with IC50 values of 2.669 and 3.596 µM, respectively.
Assuntos
Flavonoides , Sophora , Flavonoides/química , Sophora flavescens , Sophora/química , Extratos Vegetais/química , Raízes de Plantas/químicaRESUMO
Six undescribed tanshinones, (+)-2-Cl-tanshindiol C (1), (-)-2-Cl-tanshindiol C (2), (+)-tanshinoic acid D (3), (-)-tanshinoic acid D (4), (-)-tanshinoic acid E (5), and (+)-tanshinoic acid E (6), were isolated from the rhizome of Salvia miltiorrhiza Bunge. Their structures were elucidated based on the spectroscopic data (UV, IR, HR-ESI-MS, and NMR). The bioactive assays of all these compounds for the antioxidant activities in cardiomyocytes upon hypoxia stimulation were evaluated. The results suggested that compounds 5 and 6 exhibited good antioxidant activities in cardiomyocytes and the cell survival rates were 46.3% and 57.9% (10-5 mol/L), respectively.
Assuntos
Salvia miltiorrhiza , Salvia miltiorrhiza/química , Antioxidantes/farmacologia , Abietanos/farmacologia , Abietanos/química , Rizoma/química , Raízes de Plantas/químicaRESUMO
Eight new arnebinol B-based meroterpenoids ((-)-1, 2, 3, (-)-5, and 7-10) with a constrained 6/10/5 tricyclic backbone were isolated from the roots of Arnebia euchroma. The planar and steric structures of these new compounds were unambiguously elucidated by extensive spectroscopic analyses, X-ray diffraction crystallography, and ECD calculations. The predominant relative orientation between H-7 and the Z double bond with a methyl substituent in the rigid 10-membered carbocycle, along with the planar chirality of the Z double bond was analyzed and discussed for the first time. The illustration of the planar chirality derived from the Z double bond should be paid great importance during the structure elucidation on these homologous meroterpenoids. All the isolated meroterpenoids were screened for their cytotoxicities against the HCT-8, PANC-1, HGC-27, HepG2, and PC9 cell lines, and compounds (+)-5 and (-)-5 exhibited the most potent cytotoxicity.
Assuntos
Boraginaceae , Boraginaceae/química , Estrutura Molecular , Raízes de Plantas/química , Esqueleto , Terpenos/química , Terpenos/farmacologiaRESUMO
To further reveal the active ingredients of Danshen, we systematically studied its chemical components and obtained two new lithospermic acid derivatives (compounds 1 and 2) together with five known phenylpropionic acids (compounds 3-7) from the dried rhizomes of Salvia miltiorrhiza. The structures of the two new compounds were determined by multiple spectral analyses (UV, IR, HR-ESI-MS, NMR, and ECD). In addition, the absolute configurations were established by chiral analysis and calculated and experimental circular dichroism spectra. Biological research indicated that compound 1 could significantly inhibit the proliferation of isoproterenol (ISO)-treated cardiac fibroblasts (AC16 cells), and MMP9 was found to be the most likely target of compound 1. The protein expression and mRNA levels of MMP9 were increased in ISO-induced AC16 cells, which could be reversed by treatment with compound 1. Furthermore, this treatment could alleviate the migration and activation of ISO-induced cardiac fibroblasts.
Assuntos
Salvia miltiorrhiza , Descarboxilação , Metaloproteinase 9 da Matriz , Raízes de Plantas/química , Rizoma , Salvia miltiorrhiza/químicaRESUMO
A series of 4-thiosubstituted flavan derivatives (1-44) were designed and synthesized. The target compounds were assayed for inhibitory activity against α-glucosidase in vitro, and the results indicated that all compounds displayed significant effects in the range of IC50 = 1.03-7.48 µM compared to that of acarbose, the positive control drug. Structure-activity relationship (SAR) studies indicated that the hydroxyl groups in the flavan B ring, the electron withdrawing groups, and the length of the alkyl chains are important for this biological activity. In addition, some compounds were tested for their tolerance to sucrose in mice, and compound 44 exhibited activity comparable to that of acarbose. Docking analysis indicated that compound 44 binds to the enzyme in a pocket close to the catalytic site, similar to acarbose.
Assuntos
Acarbose , Inibidores de Glicosídeo Hidrolases , Acarbose/farmacologia , Animais , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismoRESUMO
Seven new phenolic acids, 7, 8-epiblechnic acid (1), 8-epiblechnic acid 9-ehthyl-9'-methyl ester (2), 9'-ehyl-isolithospermate (3), 9''-methyl-isolithospermate (4), 9'-ethyl-9''-methyl-isolithospermate (5), 9', 9''-dimethyl-isolithospermate (6), sebesteniod E (7), were isolated from the roots of Salvia miltiorrhiza. Their structures were elucidated by detailed spectroscopic means including UV, IR, HRESIMS, and NMR data spectra. The bioactive assays of compounds 1-7 against neuroprotection activities were determined. The results suggested that compound 4 exhibited a moderate glutamate-induced neuroprotective activity and the cell survival rate was 24.0% (10-5 mol/L), while compound 2 showed weak activity (survival rate: 7.58%, 10-5 mol/L), using PHPB (survival rate: 7.56%, 10-5 mol/L) as positive control.
Assuntos
Salvia miltiorrhiza , Hidroxibenzoatos/farmacologia , Estrutura Molecular , Raízes de Plantas , Salvia miltiorrhiza/químicaRESUMO
A phytochemistry of the whole plant of Agrimonia pilosa led to the discovery of two new nortriterpenoids, agrimonorterpenes A and B (1 and 2), together with one known triterpenoid fupenzic acid (3) and seven known sesquiterpenoids (4-10). The new structures were determined as 19α-hydroxy-2-oxo-nor-A (3)-urs-11,12-dien-28-oic acid (1) and 2, 19ß-dihydroxy-3-oxo-23-noroleana-1, 4, 12-trien-28-oic acid (2) by the spectroscopic data of UV, IR, HR-ESI-MS, and NMR. Notably, the structure of 1 possessed a rare five-membered A- ring. And this is the first time to discover the sesquiterpenoids (4-10) from A. pilosa. Compound 3 displayed the selective cytotoxicity against HCT116, BGC823, and HepG2 cell lines with the IC50 values of 16.31 µM, 21.94 µM, and 23.40 µM, respectively.
Assuntos
Agrimonia/química , Sesquiterpenos/isolamento & purificação , Triterpenos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/toxicidade , Espectroscopia de Ressonância Magnética , Rotação Ocular , Sesquiterpenos/química , Sesquiterpenos/toxicidade , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Triterpenos/química , Triterpenos/toxicidadeRESUMO
Five new dimeric phloroglucinol derivatives, agrimones A - E (1-5), were isolated from the whole plant of Agrimonia pilosa. Their structures including absolute configurations were determined by a series of spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR), complemented with the comparison of the experimental and calculated ECD spectra, and gauge-independent atomic orbital (GIAO) NMR calculations. Notably, compounds 1 and 2 represent a highly oxidized 6/6/6 tricyclic ring skeleton based on the cis-fused paraquinone and chroman. Compounds 1a, 4, and 5 exhibited moderate hepatoprotective activities against APAP-induced HepG2 cell injury at 10 µM.
Assuntos
Agrimonia/química , Floroglucinol/farmacologia , Substâncias Protetoras/farmacologia , Acetaminofen , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Estrutura Molecular , Floroglucinol/química , Floroglucinol/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Thirteen undescribed diterpenoid quinones were isolated from the dried roots of Salvia miltiorrhiza. Their structures were determined by extensive analysis, including NMR, HRESIMS, and IR. Their absolute configurations were determined by X-ray diffraction, calculated and experimental circular dichroism spectroscopy, and optical rotation. In the evaluation of bioactivities, salviadionether obviously inhibited the proliferation of HCT-116 cells. R-(+)-salmiltiorin E and R-(+)-grandifolia D both showed inhibitory activities on a variety of tumor cells. Salvianone ester A showed strong cytotoxicity to tumor-repopulating cells (TRCs) with an IC50 value of 2.19 µM.
Assuntos
Diterpenos , Salvia miltiorrhiza , Salvia , Diterpenos/farmacologia , Estrutura Molecular , Raízes de Plantas , Quinonas/farmacologia , RizomaRESUMO
Neuroinflammation is emerging as a crucial reason of major neurodegenerative diseases in recent years. Increasingly evidences have supported that bioactive natural products from traditional Chinese medicines have efficiency for neuroinflammation. Forsythia suspensa, a typical medicinal herb, showed potential neuroprotective and anti-inflammatory properties in previous pharmacological studies. In our research to obtain neuroprotective and anti-inflammatory natural products, three unprecedented C6-C7'/C6-C16' linked phenylethanoidglycoside dimers (1-3), three new phenylethanoidglycosides (4-6), and six known compounds (7-12) were isolated from the fruits of Forsythia suspensa. Their structures were determined by comprehensive spectroscopic data and comparison to the literature data. All isolated compounds were evaluated their neuroprotective and anti-inflammatory activities. Compounds 1 and 10 exhibited significant neuroprotective activities with the cell viability values of 75.24 ± 8.05% and 93.65 ± 10.17%, respectively, for the serum-deprivation and rotenone induced pheochromocytoma (PC12) cell injury. Meanwhile, compound 1 exhibited excellent anti-inflammatory activity against tumor necrosis factor (TNF)-α expression in LPS induced RAW264.7 cells with the IC50 value of 1.30 µM. This study revealed that the bioactive phenylethanoidglycosides may attenuate neuroinflammation through their neuroprotective and anti-inflammatory activities.
Assuntos
Anti-Inflamatórios/química , Forsythia/química , Glicosídeos/química , Fármacos Neuroprotetores/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Forsythia/metabolismo , Frutas/química , Frutas/metabolismo , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Conformação Molecular , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Células PC12 , Extratos Vegetais/química , Células RAW 264.7 , Ratos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Aiming to discover potent anti-proliferative agents from the roots of Sophora flavescens, seven new prenylated flavanones were isolated, along with 16 known compounds. Their structures were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, UV, IR, CD, and HRESIMS) and comparison to literature data. In the in vitro assay, 21 showed anti-proliferative activity against human hepatoma cells (HepG2). Studies of its mechanism revealed that 21 could significantly activate autophagic flux and trigger ROS release in HepG2 cells. Western blot experiments demonstrated that 21 could activate the key signaling protein of autophagy and ROS, while it does not affect the main protein of the apoptosis signaling pathway. These results suggested that 21 mediates its anti-proliferative effects through autophagic cell death, which is apoptosis-independent.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Flavanonas/química , Raízes de Plantas/química , Sophora/química , Animais , Autofagia/efeitos dos fármacos , Células CHO , Cricetinae , Cricetulus , Células Hep G2 , Humanos , Estrutura MolecularRESUMO
One pair of new amides enantiomers (1a and 1b) and two known amides were isolated from the rhizomes of Polygonum cuspidatum. Their structures were established using UV, IR, HRESIMS, and NMR data. Notably, compound 1 possesses unique C-C connection between feruloyltyramine and resveratrol. Their absolute configurations were determined by the ECD method. All compounds were evaluated for their α-glucosidase inhibitory activity and compounds 2 and 3 showed significant inhibitory activity with IC50 values of 2.82 and 13.06 µmol/L, respectively (positive control acarbose, IC50 385 µmol/L).
Assuntos
Fallopia japonica , Polygonum , Amidas/farmacologia , Estrutura Molecular , Extratos Vegetais , RizomaRESUMO
A concise method was established to determine the relative and absolute configurations of aryl-glycerols that depend on the chemical shift differences (Δδ) of the diastereotopic methylene protons (H-3) by 1H NMR spectroscopy. When using DMSO-d 6 as the preferred solvent, the threo configuration corresponded to a larger Δδ H3a-H3b value (>0.15 ppm), whereas the erythro configuration (<0.07 ppm) corresponded to a smaller value. Furthermore, the absolute configurations were determined with the aid of a simple acylation reaction through camphanoyl chloride. In the threo enantiomers, the Δδ value of the 1R,2R configuration was <0.15 ppm, and that of the 1S,2S configuration was >0.20 ppm. In the erythro enantiomers, the Δδ value of 1R,2S was >0.09 ppm, and that of 1S,2R was <0.05 ppm. Remarkably, this empirical rule is invalid in CDCl3. In addition, this method was also verified by a quantum 1H NMR calculation.
RESUMO
Six methyl-substituted phloroglucinol glycosides (1-6) were isolated from Agrimonia pilosa, including four new compounds (1-3, 6). The aglycones (1a-4a) of 1-4 and their corresponding oxidized products (1c-4c) were also obtained from A. pilosa. The structures were determined by a series of spectroscopic analyses and chiral separation. Notably, the structures of aglycones 1a-4a were unstable and prone to oxidation spontaneously, to yield the dearomatized structures 1c-4c. The mechanism of oxidative dearomatization was disclosed as a free-radical chain reaction with 3O2 by the techniques of HPLC-HR-MS2, EPR spectra and DFT-calculation, and hydroperoxide was defined as the intermediate.