ABSTRACT
Nine tetrahydrofuran lignans, including three undescribed spiro-lignans, were isolated from Isatis indigotica Fortune (Brassicaceae). Extensive spectroscopic analyses achieved the structure elucidation of these tetrahydrofuran lignans, and quantum chemical calculation combined with the MAEΔΔδ parameter. Notably, isatispironeols A-B have a unique spiro[dienone-tetrahydrofuran] molecular core. These spiro[dienone-tetrahydrofuran] lignans showed comparable neuroprotective effects as the positive control in the H2O2-induced SH-SY5Y cells model. In addition, (-)-(7R,8S,1'R,7'R,8'R)-isatispironeol A possessed more significant AChE inhibitory activity, further interact sites were also predicted by the in silico assay.
Subject(s)
Isatis , Lignans , Neuroblastoma , Humans , Lignans/chemistry , Isatis/chemistry , Acetylcholinesterase , Cholinesterase Inhibitors , Hydrogen Peroxide , Furans/chemistry , Molecular StructureABSTRACT
Seven undescribed polyketide compounds (1-4, 9-11) and six known polyketide compounds (5-8,12, 13) were isolated from Rhodiola tibetica endophytic Penicillium sp. HJT-A-10. The structural of seven undescribed polyketides metabolites were established on the basis of spectroscopic methods. The results of anti-inflammatory activity showed that compounds 1-8ï¼10-13 had significant inhibitory effects on LPS-induced NO production in RAW 264.7 cells.
Subject(s)
Penicillium , Polyketides , Rhodiola , Penicillium/chemistry , Molecular Structure , Anti-Inflammatory Agents/chemistryABSTRACT
UV-guided fractionation led to the isolation of thirteen new polyacetylenes (1-13) from the roots of Bupleurum scorzonerifolium Willd. All polyacetylenes were analyzed as racemates since the lack of optical activity and Cotton effects in the ECD spectra. The sequent chiral-phase HPLC resolution successfully gave twelve pairs of enantiomers 1a/1b and 3a/3b-13a/13b. Their structures were elucidated based on the HRESIMS and NMR data analyses. The absolute configurations were determined by the combination of Snatzke's method, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Using Griess methods and MTT assays, polyacetylenes 1a, 3a, 4a/4b-12a/12b, and 13a displayed inhibitory activities against LPS-induced NO release in BV-2 microglial cells.
Subject(s)
Bupleurum/chemistry , Nitric Oxide/antagonists & inhibitors , Plant Extracts/pharmacology , Polyacetylene Polymer/pharmacology , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Roots/chemistry , Polyacetylene Polymer/chemistry , Polyacetylene Polymer/isolation & purification , Stereoisomerism , Structure-Activity Relationship , Ultraviolet RaysABSTRACT
Seven alkaloids including five undescribed ones (1a/1b, 2, 3 and 5) were obtained from the leaves of Isatis indigotica Fortune. Their structures were established by extensive spectroscopic analyses. The absolute configurations of compounds 1a, 1b, 3 and 5 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Subsequently, the neuroprotective effects of all the isolates against H2O2-induced injury in SH-SY5Y cells were evaluated in vitro by MTT assay. Moreover, Annexin V-FITC/PI double staining was performed, while the activities of antioxidant enzymes (SOD, CAT and GSH-Px) for compounds 1a and 1b were measured.
Subject(s)
Alkaloids , Isatis , Neuroprotective Agents , Alkaloids/pharmacology , Hydrogen Peroxide/toxicity , Molecular Structure , Neuroprotective Agents/pharmacology , Plant LeavesABSTRACT
In the current study, four pairs of new enantiomeric alkaloids (1a/1b-4a/4b) were obtained from the leaves of Isatis indigotica Fortune Ex Land. Their structures were elucidated through spectroscopic methods and quantum mechanical calculations. Biologically, all isolates were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury. As a result, 1a and 1b exhibited enantioselective neuroprotective effects, further Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 20.93% and 17.87%, respectively.
Subject(s)
Alkaloids/pharmacology , Hydrogen Peroxide/metabolism , Isatis/chemistry , Neurons/drug effects , Neuroprotective Agents/pharmacology , Alkaloids/chemistry , Apoptosis/drug effects , Cell Line , Humans , Neurons/cytology , Neurons/metabolism , Neuroprotective Agents/chemistry , Plant Leaves/chemistry , StereoisomerismABSTRACT
Six pairs of alkaloid enantiomers including 11 new alkaloids (1A: /1B: -5A: /5B, 6A: ) were isolated from the leaves of Isatis tinctoria. Their structures were established by extensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and the absolute configurations of all isolates were determined by comparison of experimental and calculated electronic circular dichroism spectra. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that 5A/5B: and 6A/6B: exhibited potent neuroprotective activities at 50 µM compared with the H2O2-treated group.
Subject(s)
Isatis/chemistry , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Cell Line, Tumor , Humans , Hydrogen Peroxide , Isomerism , Molecular Structure , Neuroblastoma , Neurons/drug effects , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purificationABSTRACT
Five pairs of enantiomeric compounds (1a/1b-5a/5b) including seven undescribed compounds (1a/1b-3a/3b, 4b) along with two known ones (. and .) have been isolated from corn silk (Stigma maydis). Racemic mixtures of these enantiomers were separated by HPLC with different types of chiral columns. Their structures were elucidated based on comprehensive spectroscopic analyses together with quantum chemical calculations of 13C NMR data and electronic circular dichroism (ECD) curves. All the isolates were evaluated for their inhibition ability of self-induced Aß1-42 aggregation. Among them, compounds 4a (88.36%), 4b (74.66%) and . (85.65%) showed stronger inhibitory activity than the positive control curcumin (61.90%). The different inhibition profiles of enantiomers 4a and 4b were explained by docking simulation studies.
Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Flowers/chemistry , Peptide Fragments/antagonists & inhibitors , Phytochemicals/pharmacology , Protein Aggregation, Pathological/prevention & control , Zea mays/chemistry , China , Molecular Docking Simulation , Molecular Structure , Phytochemicals/isolation & purificationABSTRACT
A pair of new cycloneolignan enantiomers (1a and 1b) were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated by extensive spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, MS/MS analysis, together with theoretical electronic circular dichroism (ECD) calculations. Compounds 1a and 1b were then evaluated for their neuroprotective effects against MPP+-induced SH-SY5Y cell injury. As a result, compounds 1a (77.64%) and 1b (78.62%) exhibited moderate neuroprotective activity at the concentration of 12.5⯵M compared with that of MPP+ treated group (62.00% at 1â¯mM) by MTT assay. Furthermore, Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 10.99% and 9.31%, respectively.
Subject(s)
1-Methyl-4-phenylpyridinium/antagonists & inhibitors , Drug Discovery , Isatis/chemistry , Lignans/pharmacology , Neuroprotective Agents/pharmacology , 1-Methyl-4-phenylpyridinium/pharmacology , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Lignans/chemistry , Lignans/isolation & purification , Molecular Structure , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Plant Leaves/chemistry , Stereoisomerism , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Correction for 'Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica fortune' by Si-Fan Liu et al., Org. Biomol. Chem., 2018, 16, 9430-9439.
ABSTRACT
Four pairs of new spiropyrrolizidine oxindole enantiomers (1a/1b-4a/4b) were isolated from the leaves of Isatis indigotica Fortune. Their structures and absolute configurations were elucidated by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD) and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Notably, all the isolated spiropyrrolizidine oxindoles are reported as natural products for the first time. The biosynthetic pathway of these unique structures was proposed to be formed by cycloaddition reaction. In addition, all the compounds were evaluated for their inhibitory effects on ß-amyloid aggregation by ThT assay, and the optically pure compounds 1a/1b and 2a/2b exhibited better Aß1-42 aggregation inhibition potency (85.8% and 73.6%, 71.5% and 75.8%, respectively) at a concentration of 20 µM, compared with the positive control curcumin (57.0%). The difference of the inhibitory pattern caused by chirality was also explained by molecular docking studies.
Subject(s)
Isatis/chemistry , Oxindoles/chemistry , Pyrrolizidine Alkaloids/chemistry , Spiro Compounds/chemistry , Amyloid beta-Peptides/metabolism , Humans , Molecular Docking Simulation , Oxindoles/isolation & purification , Oxindoles/pharmacology , Peptide Fragments/metabolism , Protein Aggregates/drug effects , Pyrrolizidine Alkaloids/isolation & purification , Pyrrolizidine Alkaloids/pharmacology , Spiro Compounds/isolation & purification , Spiro Compounds/pharmacology , StereoisomerismABSTRACT
Seven new N-acylanthranilic acid derivatives (1-3, 4a/4b, 5a/5b) including two pairs of enantiomers (4a/4b and 5a/5b) were isolated from the leaves of Isatis indigotica Fortune. Their chemical structures were elucidated by extensive spectroscopic data analyses. The absolute configurations of compounds 4a/4b and 5a/5b were determined by comparison of the experimental and calculated ECD spectra. All compounds were tested for their anti-Aß1-42 aggregation activity. As a result, compounds 1 (72.1%), 2 (79.8%) and 5a (81.8%) showed stronger inhibitory activity than the positive control curcumin (67.0%). By the comparison between 5a (81.8%) and 5b (63.1%), it was found that stereochemical configurations may affect Aß1-42 aggregation activity, which was discussed through the molecular docking results of compounds 5a and 5b.
Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Isatis/chemistry , Peptide Fragments/antagonists & inhibitors , Plant Leaves/chemistry , ortho-Aminobenzoates/isolation & purification , Molecular Docking Simulation , StereoisomerismABSTRACT
Rubus ideaus L., a member of the Rosaceae family, is popular for its distinctive flavor and attractive red color. In order to explore the functional factors possibly presented in the fruit, seven new benzofuran neolignans (1a/1b-3a/3b and 4b), together with one known neolignan 4a, were isolated from the fruit of R. ideaus. Compounds 1a/1b-4a/4b as four pairs of enantiomers were separated on a chiral chromatographic column. Their structures including absolute configurations were elucidated by extensive spectroscopic data analyses, including UV, IR, HRESIMS, NMR, and comparing their experimental electronic circular dichroism (ECD) spectra with calculated ECD spectra. Additionally, all these enantiomeric compounds were evaluated for their antioxidant, neuroprotective, and anti-Aß1-42 aggregation activities.
Subject(s)
Benzofurans/chemistry , Fruit/chemistry , Lignans/chemistry , Rubus/chemistry , Amyloid beta-Peptides/chemistry , Cell Line, Tumor , Circular Dichroism , Free Radical Scavengers/chemistry , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Peptide Fragments/chemistry , StereoisomerismABSTRACT
Enantiomers account for quite a large percentage of compounds in natural products. Our team is interested in the separation and biological activity of racemic compounds. In this report, four pairs of prenylated flavan enantiomers [(±)-1-(±)-4], including five new compounds, were isolated from the stem and root bark of Daphne giraldii, and separated successfully by using chiral chromatographic column. Their planar structures and absolute configurations were established by comprehensive spectroscopic analyses as well as circular dichroism (CD) spectroscopy. The isolates had a selective cytotoxicity towards hepatic carcinoma cell lines. Among them, new compound (+)-4 showed a more potent inhibitory effect on Hep3B cells with an IC50 value of 30.3 µM, compared with its racemic mixture 4. Therefore, the action mechanism of (+)-4in vitro was subsequently investigated. The morphological observation and Western blot analysis demonstrated that (+)-4 could markedly induce apoptosis through intrinsic and extrinsic pathways, and also cause autophagy by increasing the phosphorylation of AMP-activated protein kinase (AMPK) in Hep3B cells. After treatment with the autophagic inhibitor bafilomycin A1 (Baf A1), (+)-4-induced apoptosis increased significantly, suggesting that the autophagy induced by (+)-4 performed a protective effect on apoptotic cell death.
