ABSTRACT
Two previously undescribed chain diarylheptanoid derivatives (2-3), five previously undescribed dimeric diarylheptanoids (4-8), together with one known cyclic diarylheptanoid (1) were isolated from Zingiber officinale. Their structures were elucidated by extensive spectroscopic analyses (HR-ESI-MS, IR, UV, 1D and 2D NMR) and ECD calculations. Biological evaluation of compounds 1-8 revealed that compounds 2, 3 and 4 could inhibit nitrite oxide and IL-6 production in lipopolysaccharide induced RAW264.7 cells in a dose-dependent manner.
Subject(s)
Zingiber officinale , Diarylheptanoids/pharmacology , Diarylheptanoids/chemistry , Magnetic Resonance Spectroscopy , Anti-Inflammatory Agents/pharmacology , Molecular StructureABSTRACT
Eight previously undescribed lanostane triterpenoids and nine known ones were identified from the fruiting bodies of Ganoderma lingzhi S.H. Wu, Y. Cao & Y.C. Dai. Their structures were determined based on spectroscopic data and quantum chemical calculations. Structurally, ganoderane GL-1, featuring a hydrogenated tetramethyls-phenanthraquinone, represents the first example in lanostane nor-triterpenoid group. Biologically, ganoderanes GL-2 and GL-3, distinguished by the presence of a rare "1,11-epoxy" moiety, exhibited significant inhibition against nitric oxide production induced by lipopolysaccharide in RAW264.7 macrophage cells, while ganoderanes GL-4 and GL-8 exhibited bifunctional activities of anti-proliferation and anti-inflammation.
Subject(s)
Agaricales , Ganoderma , Triterpenes , Triterpenes/pharmacology , Triterpenes/chemistry , Molecular Structure , Fruiting Bodies, Fungal/chemistry , Ganoderma/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Steroids/analysisABSTRACT
Six new flavonols, including four glucosylated flavonols (dysosmaflavonoid A-D), one phenylpropanoid-substituted flavonol (dysosmaflavonoid E), and one phenyl-substituted flavonol (dysosmaflavonoid F), together with five known analogues, were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HRESIMS, and HPLC data. The antioxidant activities of all isolated compounds were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 2, 3, 5-8, and 12 exhibited significant DPPH scavenging capacity with IC50 values of 33.95, 39.02, 31.17, 32.79, 31.85, 30.48, and 23.75 µM, respectively, in comparison with Trolox (IC50, 15.80 µM). Compound 12 displayed more potent DPPH radical scavenging activity than prenylated and (or) glucosided derivatives (2-4, or 10). The preliminary structure-activity relationship showed that the catechol structure in flavonol is essential for DPPH radical scavenging effect.
Subject(s)
Berberidaceae , Flavonols , Flavonols/pharmacology , Flavonols/chemistry , Molecular Structure , Antioxidants/pharmacology , Antioxidants/chemistry , Berberidaceae/chemistry , Structure-Activity Relationship , Free Radical Scavengers/chemistry , Biphenyl Compounds , Picrates/chemistryABSTRACT
One new 6a,11a-dehydropterocarpan derivative, 6-O-methyl-anhydrotuberosin (1), one new 6a-hydroxypterocarpan, (6aR,11aR,11bR)-hydroxytuberosone (7), and seven known compounds including two 6a,11a-dehydropterocarpans (2 and 4), two coumestans (3 and 5), one isoflavonoid (6) and two other phenolic compounds (8 and 9) were isolated from the roots of Pueraria lobata. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods (1 D and 2DNMR, HRESIMS). Compounds 1, 2, 4-5 showed potent LSD1 inhibitory activities with IC50 values ranging from 1.73 to 4.99 µM. Furthermore, compound 2 showed potent cytotoxicity against gastric cancer cell lines MGC-803 and BGC-823, and lung cancer cell lines H1299 and H460.
Subject(s)
Isoflavones , Pueraria , Pueraria/chemistry , Cell Line , Phenols , Histone Demethylases/analysis , Plant Roots/chemistry , Isoflavones/pharmacology , Isoflavones/chemistryABSTRACT
Two new guaianolide-type sesquiterpenoids chrysanthemulides K and L (1 and 2), together with six known analogues (3-8), were isolated from an CH2Cl2 extract of the aerial parts of Chrysanthemum indicum. The structures of new compounds 1 and 2 were established by extensive spectroscopic analysis, including UV, IR, MS, NMR and computational electronic circular dichroism (ECD) methods. Inhibitory effects of all compounds on nitric oxide production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 1-8 displayed NO production inhibitory activity with IC50 values ranged from 3.5 to 34.3 µM.
Subject(s)
Chrysanthemum , Sesquiterpenes , Animals , Mice , Chrysanthemum/chemistry , RAW 264.7 Cells , Sesquiterpenes/chemistry , Plant Extracts/pharmacology , Magnetic Resonance Spectroscopy , Nitric Oxide , Molecular Structure , Lipopolysaccharides/pharmacologyABSTRACT
Five pairs of new biflavonoid enantiomers, (±)-dysosmabiflavonoids A-E (1-5), two new biflavonoids, dysosmabiflavonoids F-G (6-7), and four biosynthetically related precursors (8-11) were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by extensive spectroscopic analysis, including HR-ESI-MS and 2D NMR. Their absolute configurations were determined by comparison of the calculated and experimental ECD spectra. All isolated compounds were evaluated for AChE inhibitory activity. Compounds 6 and 7 exhibited more potent inhibitory activities with IC50 values of 1.42 and 0.73 µM, respectively, than their biosynthetically related precursors kaempferol (8, 17.90 µM) and quercetin (9, 3.96 µM). The preliminary structure-activity relationship study indicated that the connection mode of biflavonoid subunits, oxidation degree of the C ring, and 3,4-dihydroxy group of the B ring were important structural factors for AChE inhibitory activity. Racemates 1-5 and their corresponding levorotatory and dextrorotatory enantiomers were tested for their potential to impede the generation of NO in lipopolysaccharide-stimulated RAW264.7 cells, and their mushroom tyrosinase inhibitory effect. Racemate 1 displayed more potent mushroom tyrosinase inhibitory activity (IC50, 28.27 µM) than the positive control kojic acid (IC50, 32.59 µM). D. versipellis may have therapeutic potential for melanogenesis disorders and neurodegenerative diseases.
ABSTRACT
Eighteen linear triquinane sesquiterpenoids (LTSs), including seventeen previously undescribed ones (hirsutuminoids A-Q), were isolated from the fermentation of the fungus Stereum hirsutum (Willd.) Pers. The structures and absolute configurations of the isolates were characterized by extensive spectroscopic analysis (1D, 2D NMR, and HRMS data), together with comparing the experimental and calculated data of both electronic circular dichroism and NMR data, as well as X-ray crystallography. Based on the literature survey and efforts on constructing the absolute configurations of these LTSs in this study, one empirical rule about the orientations of substitutions at C-2/C-3/C-7/C-9 was summarized. Anti-inflammatory and cytotoxic bioassays showed that only hirsutuminoid B inhibited the nitric oxide (NO) production in RAW 264.7 macrophages with an IC50 value, 18.9 µM.
Subject(s)
Basidiomycota , Sesquiterpenes , Basidiomycota/chemistry , Crystallography, X-Ray , Molecular Structure , Nitric Oxide , Sesquiterpenes/chemistryABSTRACT
Investigation into the chemical diversity of Nardostachys chinensis Batal led to the discovery of three new (1-3) and one known (4) iridoid glycosides. Their structures were established through spectroscopic methods including 1 D and 2 D NMR experiments and HRESIMS analysis. Inhibitory effects of 1-4 on nitric oxide production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and they displayed IC50 values in the range 7.8-15.2 µM.
Subject(s)
Nardostachys , Animals , Glycosides/pharmacology , Iridoid Glycosides/pharmacology , Magnetic Resonance Spectroscopy , Mice , Nardostachys/chemistry , Nitric Oxide , RAW 264.7 CellsABSTRACT
[This corrects the article DOI: 10.1039/D1RA05204G.].
ABSTRACT
Two new monoterpene indole alkaloid glycosides nutanoside A-B (1-2), two new phenolic glycoside esters nutanester A-B (6-7), together with five known compounds (3-5, 8-9) were isolated from the ethanol extract of Gardneria nutans Siebold & Zuccarini. Their structures were established on the basis of extensive spectroscopic analysis and TDDFT/ECD calculations. Compounds 1 and 2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids. Compounds 3, 4 and 6 displayed significant inhibitory effects on NO production in over-activated BV2 microglial cells, with the IC50 values of 2.29, 6.36, and 8.78 µM, respectively. Compounds 1, 5, 7 could significantly inhibit the mRNA expression of inflammatory factors TNF-α and IL-6 induced by LPS in BV2 microglial cells at the effective concentration. Moreover, compound 3 exhibited stronger cytotoxicities against U87 and HCT116 cell lines than taxol with IC50 values of 10.58 and 14.60 µM, respectively.
ABSTRACT
Fourteen new polyhydroxylated pregnane glycosides, cissasteroid A-N (1-14), and five known analogues (15-19), were isolated from the dried whole plant of Cissampelos pareira var. hirsuta. Their structures and stereochemistry were elucidated by extensive spectroscopic data, chemical hydrolysis, and ECD measurements. All the compounds were tested for their cytotoxicity against five human cancer cell lines, and inhibitory activity against NO release in LPS-induced RAW 264.7 cells. Compared with cisplatin, compound 7 showed more potent cytotoxicities against the HL-60, A549, SMMC-7721, MCF-7, and SW480 cell lines, with IC50 values of 2.19, 14.38, 2.00, 7.58, and 7.44 µM, respectively. The preliminary study of structure-activity relationship indicated that benzoic acid esterification at C-20 may have a negative effect on the cytotoxic activity of polyhydroxylated pregnane derivatives in these five human cancer cell lines. These results revealed the potential of compound 7 as an ideal antitumor lead compound.
ABSTRACT
Ochracines A-E, five previously undescribed norsesquiterpenes featured by unusual scaffolds biogenetically related to chamigrane, were isolated from the cultures of Steccherinum ochraceum. Ochracines A (1) and B (2) represent the first examples of norsesquiterpenes with an unprecedented 1,2-6,7-diseco-1,8-cyclochamigrane scaffold. Ochracines C-D (3-5) possess an unusual 1,2-6,7-diseco-chamigrane skeleton. Their structures were elucidated by analysis of spectroscopic data. The absolute configuration of ochracine A (1), and the relative configuration of ochracine B (2) were determined by ECD and/or NMR calculations. The biosynthetic pathways for the norsesquiterpenes were proposed. All isolates were evaluated for their cytotoxicity against the five human cancer cell lines HL-60, SMMC-7721, A549, MCF-7, and SW-480.
Subject(s)
Polyporales/chemistry , Sesquiterpenes/pharmacology , Cell Line, Tumor , China , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Sesquiterpenes/isolation & purificationABSTRACT
Six new coumarin glycosides, genglycoside A-F (1-6), were isolated from the aerial parts of Gendarussa vulgaris, along with ten known analogues (7-16). Their structures were unambiguously established on the basis of extensive spectroscopic data and HPLC analysis. The cytotoxic activities of all isolated compounds were evaluated by MTT assay. Compound 12 showed the most potent cytotoxicity in Eca-109, MCF-7, and HepG2 cell lines. By the preliminary structure-activity relationships, it was firstly discovered that the glycosylation or esterification at 7,8-dihydroxy or 7-hydroxy drastically reduced the cytotoxic activity of the parent coumarin.
Subject(s)
Antineoplastic Agents, Phytogenic , Coumarins , Glycosides , Lamiales/chemistry , Plant Components, Aerial/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Coumarins/chemistry , Coumarins/isolation & purification , Coumarins/pharmacology , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Hep G2 Cells , Humans , MCF-7 CellsABSTRACT
Three new tetralol analogs, myrochromanols A-C (1-3), together with 11 known trichothecenes (4-14), were isolated from a soil fungus Myrothecium verrucaria HL-P-1. The structures of the three new compounds were elucidated by extensive spectroscopic analysis including HRESIMS, NMR, and ECD calculation. All of the new compounds were tested for their anti-inflammatory activity and cytotoxicity. Compounds 1 and 3 inhibited lipopolysaccharide (LPS)-induced NO production in BV2 cells with IC50 values of 26.04 and 25.80 µM, respectively.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Hypocreales/metabolism , Soil Microbiology , Tetralones/isolation & purification , HL-60 Cells , Humans , Tetralones/chemistry , Tetralones/pharmacologyABSTRACT
A new fumiquinazoline-type alkaloid 2-methyl-versiquinazoline C (1), together with six known compounds (2-7), was isolated from Aspergillus flavipes PJ03-11 using OSMAC method. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configuration of compound 1 was determined by the experimental and calculated ECD data. In addition, the cytotoxic activities against three human cancer cell lines (HL-60, THP-1, and PC-3) were evaluated.
Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Aspergillus/chemistry , Quinazolines/chemistry , Quinazolines/pharmacology , Cell Line, Tumor , Fermentation , HL-60 Cells , Humans , Molecular StructureABSTRACT
Two new C21 steroidal glycosides, cynataihosides E (1) and F (2), together with a known one, sublanceoside H2 (3), were isolated from Cynanchum taihangense. The aglycone of cynataihoside F (2) was also a new compound. Their structures were elucidated on the basis of NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. Their cytotoxic activities against three human tumor cell lines (HL-60, THP1, and Caco2) were reported.
Subject(s)
Cynanchum/chemistry , Glycosides/isolation & purification , Steroids/isolation & purification , Caco-2 Cells , Glycosides/chemistry , Glycosides/pharmacology , HL-60 Cells , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistry , Steroids/chemistry , Steroids/pharmacologyABSTRACT
Because of the critical role of over-activated microglia in the progress of neurodegenerative diseases, it has been selected as a potential therapeutic target for drug discovery. In order to find natural neuroinflammatory inhibitors, we carried out a bioactivity-oriented phytochemical research of Caragana turfanensis Kom. (Krassn.), which is a folk medicine widely distributed in Xinjiang. As a result, a new coumarin lactone caraganolide A (1) and 35 known components were characterized from the effective extract of C. turfanensis. Furthermore, their anti-neuroinflammatory effects were evaluated in LPS-induced BV2 microglial cells using Griess assay to determine the release of nitric oxide (NO). Compounds 1, 2, 4-6, 9, 13-15, 20, 29 and 30 exhibited significant inhibitory activities and no obvious cytotoxicities were observed at their effective concentrations. It is noteworthy, the new compound caraganolide A (1) (IC50 1.01±1.57µM) and 3',7,8-trihydroxy-4'-methoxyisoflavone (5) (IC506.87±2.23µM) exhibited more excellent action than that of positive control minocycline (IC50 9.07±0.86µM).
Subject(s)
Anti-Inflammatory Agents/chemistry , Caragana/chemistry , Coumarins/chemistry , Plant Extracts/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Caragana/metabolism , Cell Line , Coumarins/isolation & purification , Coumarins/metabolism , Inhibitory Concentration 50 , Lipopolysaccharides/toxicity , Magnetic Resonance Spectroscopy , Microglia/cytology , Microglia/drug effects , Microglia/metabolism , Molecular Conformation , Nitric Oxide/metabolismABSTRACT
Neuroinflammation mediated by microglia cells plays a critical role in the development of Alzheimer's disease. To identify novel natural neuroinflammation inhibitors, a bioactivity-guided phytochemical research was performed on the traditional Chinese medicine "Awei", that exhibited a significant inhibitory effect on nitric oxide production in over-activated microglia cells. The research identified sixteen bioactive sesquiterpene coumarins (two new and fourteen known ones) in the effective extract of Ferula sinkiangensis. Further, the anti-neuroinflammatory activities in BV-2 microglial cells were evaluated by monitoring LPS-induced nitric oxide production. In conclusion, the major constituent, (3'S, 5'S, 8'R, 9'S, 10'R)-kellerin (1.5â%, w/w), should be responsible for the anti-neuroinflammatory effect exhibited by Awei. Furthermore, it might be a potential natural therapeutic agent for Alzheimer's disease. The research indicated moreover, that its primary mechanism is the inhibition of mRNA expression of the inflammatory cytokines nitric oxide, tumor necrosis factor-α, cyclooxygenase-2, interleukin-6 and interleukin-1ß.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Coumarins/pharmacology , Ferula/chemistry , Neuroprotective Agents/pharmacology , Resins, Plant/chemistry , Sesquiterpenes/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cell Line , Coumarins/chemistry , Coumarins/isolation & purification , Cytokines/metabolism , Inflammation/drug therapy , Lipopolysaccharides/adverse effects , Mice , Microglia/drug effects , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Nitric Oxide/metabolism , RNA, Messenger/genetics , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purificationABSTRACT
Five chalcanes ((α'R)-2, α'-dimethoxy-furano-[4â³, 5'': 3', 4'] chalcane, (α'R, ßR)-2', α', ß-trimethoxy-furano-[4â³, 5'': 3', 4'] chalcane, (α'S, ßR)-2', α', ß-trimethoxy-furano-[4â³, 5'': 3', 4'] chalcane, (α'R, ßR)-2', ß-dimethoxy-α'-hydroxyethoxy-furano-[4â³, 5'': 3', 4'] chalcane, (α'S, ßR)-2', ß-dimethoxy-α'-hydroxyethoxy-furano-[4â³, 5'': 3', 4'] chalcane) and a flavonoid glycoside (3', 7-dihydroxy-6-methoxy-4', 5'-methylenedioxyisoflavone 6-O-ß-D- glucopyranoside), together with 15 known components, were isolated from the leaves of Millettia pulchra (Benth) Kurzvar-laxior (Dunn) Z. Wei, a traditional Zhuang medicine. Their chemical structures were established by extensive analysis of NMR, mass spectrometry and ECD spectra. Furthermore compounds (α'R, ßR)-2', ß-dimethoxy-α'-hydroxyethoxy-furano-[4â³, 5'': 3', 4'] chalcane, (α'S, ßR)-2', ß-dimethoxy-α'-hydroxyethoxy-furano-[4â³, 5'': 3', 4'] chalcane, quercetin, methyl 2-O-ß-D-glucopyranosylbenzoate, 6,7-dimethoxy-3',4'-methylenedioxyisoflavone and lyoniresinol were suggested to be potential chemopreventive agents because of their significant activity in inducing NQO1 ([NAD(P)H quinine oxidoreductase 1], a phase II metabolism enzyme).
Subject(s)
Anticarcinogenic Agents/isolation & purification , Anticarcinogenic Agents/pharmacology , Benzofurans/isolation & purification , Benzofurans/pharmacology , Chalcones/isolation & purification , Chalcones/pharmacology , Millettia/chemistry , NAD(P)H Dehydrogenase (Quinone)/antagonists & inhibitors , Anticarcinogenic Agents/chemistry , Benzofurans/analysis , Benzofurans/chemistry , Chalcones/chemistry , Glycosides/analysis , Humans , Medicine, Traditional , Molecular Structure , Plant Leaves/chemistry , Plant Roots/chemistryABSTRACT
The total salvianolic acids are main effective constituents of Salvia miltiorrhiza Bge., a traditional Chinese medicine used for thousands of years. The purpose of present study was to make clear the composition and bioactivities of the minor components of the total salvianolic acids injection. As a result, three new minor phenolic acids (1-3) together with six known compounds (4-9) were characterized from the total salvianolic acids injection. Their structures were elucidated by extensive analysis of the spectral data. The absolute configuration of compounds 1-3 were confirmed by their J7',8' observed in (1)H NMR spectra, absorption band at approximately 250-260nm in their CD spectra as well as chemical shifts of C-8â³ and C-8â´ displayed in (13)C NMR spectra. Then DPPH free radical scavenging assay and NAD(P)H: quinine oxidoreductase 1 (NQO1) inducing activity test were employed to evaluate the antioxidant effect of new minor compounds 1 and 2. Compound 2 showed significant NQO1 inducing activity at 20µM with IR value 2.6. Meanwhile, DPPH scavenging assay revealed that the inhibition rates of compounds 1 and 2 were 84.3% and 74.9% at 2mM, respectively.