ABSTRACT
Penicisteckins A-D (1-4), two pairs of atropodiastereomeric biaryl-type hetero- and homodimeric bis-isochromans with 7,5'- and 7,7'-linkages and a pair of atropodiastereomeric 2-(isochroman-5-yl)-1,4-benzoquinone derivatives [penicisteckins E (5) and F (6)], were isolated from the Penicillium steckii HNNU-5B18. Their structures including the absolute configuration were determined by extensive spectroscopic and single-crystal X-ray diffraction analysis and TDDFT-ECD calculations. Both the bis-isochromans and the isochroman/1,4-benzoquinone conjugates represent novel biaryl scaffolds containing both central and axial chirality elements. The monomer anserinone B (8) exhibited potent antibacterial activities against Staphylococcus aureus ATCC 29213 and methicillin-resistant Staphylococcus aureus with minimal inhibition concentration values ranging from 2 to 8 µg mL-1. Plausible biosynthetic pathways of 1-6 are proposed, which suggest how the absolute configurations of the isolates were established during the biosynthetic scheme.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Chromans/isolation & purification , Penicillium/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biosynthetic Pathways , Chromans/chemistry , Chromans/pharmacology , Staphylococcus aureus/drug effectsABSTRACT
Baeyer-Villiger (BV) oxidation is a fundamental organic reaction, whereas the hetero-BV oxidation is uncharted. Herein, a tellura-BV oxidation is discovered. By oxidizing a tellurophene-embedded and electron-rich polycycle (1) with mCPBA or Oxone, an oxygen atom is inserted into the Te-C bond of the tellurophene to form tellurinate lactone mono-2. This reaction proceeds as follows: (i) 1 is oxidized to the tellurophene Te-oxide form (IM-1); (ii) IM-1 undergoes tellura-BV oxidation to give mono-2. Moreover, the hybrid trichalcogenasumanenes 7 and 8 are, respectively, converted to tellurinate lactones mono-9 and mono-10 under the same conditions, indicating that tellura-BV oxidation shows high chemoselectivity. Due to the strong secondary bonding interactions between the Te[double bond, length as m-dash]O groups on tellurinate lactones, mono-2, mono-9, and mono-10 are dimerized to form U-shaped polycycles 2, 9, and 10, respectively. Notably, mono-2, mono-9, mono-10, and their dimers show chirality. This work enables one-step transformation of tellurophene into tellurinate lactone and construction of intricate polycycles.
ABSTRACT
Two novel heptanornemoralisin-type diterpenoids nornemoralisins A (1) and B (2), together with two known compounds nemoralisin (3) and nemoralisin A (4), were isolated from the stem bark and leaves of Aphanamixis polystachya (Wall.) R. Parker. Their structures were established through comprehensive analyses of NMR spectroscopic data and high resolution mass spectrometric (HR-ESI-MS) data. The absolute configurations of carbon stereocenters were elucidated by circular dichroism (CD) analyses. The four compounds were tested for their potential cytotoxic effects against ACHN, HeLa, SMMC-7721, and MCF-7 cell lines. Nornemoralisins A (1) and B (2) exhibited significant cytotoxicity on ACHN with an IC50 value of 13.9 ± 0.8 and 10.3 ± 0.4 µM, respectively, and other compounds failed to reveal obvious cytotoxicity on the tested cell lines, compared to positive control vinblastine (IC50, 28.0 ± 0.9 µM).
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Meliaceae/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , China , Diterpenes/isolation & purification , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Bark/chemistry , Plant Leaves/chemistryABSTRACT
Xanthohumol (XN) exerts a specific cytotoxicity in B16-F10 melanoma cells with cytoplasmic vacuoles formation. Further investigation showed XN inhibited cell proliferation in a time- and dose-dependent manner along with down-regulation of mitogen-activated protein kinase and up-regulation of the endoplasmic reticulum (ER) stress marker Bip, CHOP and protein ubiquitination, which was relieved by the ER-stress inhibitor 4-PBA. Whereas no early apoptosis characteristics was identified during XN induced cell death. [Formula: see text].
Subject(s)
Endoplasmic Reticulum Stress , Propiophenones , Animals , Apoptosis , Cell Death , Cell Line, Tumor , Flavonoids , Mice , Molecular Structure , Transcription Factor CHOPABSTRACT
A new isopimarane-type diterpenoid, crolaevinoid A, along with four known analogues was isolated from the twigs and leaves of Croton laevigatus. The structures of the isolated compounds were established on the basis of NMR and MS spectroscopic analyses. The isolated compounds were examined the antibacterial activities. Unfortunately, the compounds showed no antibacterial activity against Micrococcus luteus, Methicillin-resistant Staphylococcus aureus, Aeromonas hydrophila, Klebsiella pneumoniae ssp pneumoniae, Acinetobacter Baumanii, and Escherichia coli.
Subject(s)
Abietanes/chemistry , Anti-Bacterial Agents/pharmacology , Croton/chemistry , Diterpenes/chemistry , Diterpenes/pharmacology , Anti-Bacterial Agents/chemistry , Diterpenes/isolation & purification , Drug Evaluation, Preclinical , Magnetic Resonance Spectroscopy , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Molecular Structure , Plant Leaves/chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
Vicia sativa L. (common vetch) is a potential food source for both human beings and animals because of its abundant nutritional composition. There is a lack of phytochemical study on the whole plant, and thus the objective of this study was to investigate the isolation of phytochemicals and evaluate their biological activities. A new flavanol, (2R,3S)-3,3'-dihydroxy-4',7-dimethoxyflavanol (1), together with nine known compounds, two flavones (2-3), one coumarin (4), and six oleanane triterpenoids (5-10), was obtained from Vicia sativa L.. The structure of the new compound 1 was determined via its NMR spectra, IR and CD data. Compound 3 displayed the potential of the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging effect in antioxidant test. In terms of cytotoxic activities, compound 3 showed moderate cytotoxic activities against three human tumor cells, especially HeLa cells.
Subject(s)
Antioxidants/pharmacology , Phytochemicals/pharmacology , Vicia sativa/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/chemistry , Circular Dichroism , Flavones/analysis , HL-60 Cells , HeLa Cells , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Phytochemicals/analysis , Phytochemicals/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Stems/chemistry , Triterpenes/analysisABSTRACT
Three new iridoids, rel-(4aR,7S,7aS)-7-hydroxy-7-methyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carbaldehyde (1), 1-methoxy-7-methyl-1,3,5,6-tetrahydrocyclopenta[c]pyran-4-carbaldehyde (2), and rel-(1R,4S,4aS,7R,7aR)-7-methylhexahydro-1,4-(epoxymethano)cyclopenta[c]pyran-3(1H)-one (3), together with seven known analogues, were isolated from the 95 % EtOH extract of the whole plants of Pedicularis uliginosa Bunge. Their structures were elucidated via extensive NMR spectroscopy and mass spectral data. In terms of inhibitory effects on human tumor cells, compounds 1, 2, 6, 7, and 8 exhibited better inhibitory activities against ACHN cells than the positive control (vinblastine).
Subject(s)
Iridoids/isolation & purification , Pedicularis/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Humans , Iridoids/chemistry , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Structure-Activity RelationshipABSTRACT
Lomaiviticin A and difluostatin A are benzofluorene-containing aromatic polyketides in the atypical angucycline family. Although these dimeric compounds are potent antitumor agents, how nature constructs their complex structures remains poorly understood. Herein, we report the discovery of a number of fluostatin type dimeric aromatic polyketides with varied C-C and C-N coupling patterns. We also demonstrate that these dimers are not true secondary metabolites, but are instead derived from non-enzymatic deacylation of biosynthetic acyl fluostatins. The non-enzymatic deacylation proceeds via a transient quinone methide like intermediate which facilitates the subsequent C-C/C-N coupled dimerization. Characterization of this unusual property of acyl fluostatins explains how dimerization takes place, and suggests a strategy for the assembly of C-C and C-N coupled aromatic polyketide dimers. Additionally, a deacylase FlsH was identified which may help to prevent accumulation of toxic quinone methides by catalyzing hydrolysis of the acyl group.
Subject(s)
Biosynthetic Pathways , Models, Chemical , Polyketides/chemistry , Polyketides/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Catalysis , Dimerization , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Polyketides/pharmacology , Protein Conformation , Streptomyces/genetics , Streptomyces/metabolismABSTRACT
Pyrazolofluostatins A-C (1-3), three new benzo[a]fluorenes with an unprecedented carbon skeleton, were obtained from the South China Sea-derived Micromonospora rosaria SCSIO N160. Their structures were elucidated by extensive spectroscopic analyses. The structure of pyrazolofluostatin A (1) was confirmed by X-ray crystallographic analysis. Notably, 1-3 possessed a benzo[cd]indeno[2,1-f]indazol skeleton with a pyrazole-fused 6/5/6/6/5 pentacyclic ring system. Pyrazolofluostatin A (1) showed moderate antioxidation activity (EC50 48.6 µM).
Subject(s)
Pyrazoles/chemistry , China , Fluorenes , Micromonospora , Molecular StructureABSTRACT
Euphorpekone A (1) and euphorpekone B (2), two new diterpenoids, 3ß-hydroxy-25-methyloxylanosta-8,23-diene, a new triterpenoid (3), together with a known triterpenoid, 3ß,25-dihydroxylanosta-8,23-diene (4), were isolated from Euphorbia pekinensis Rupr. Their structures were elucidated on the basis of UV, IR, 1D ((1)H, (13)C, NOE) and 2D ((1)H-(1)H COSY, HSQC, HMBC) NMR, HR-ESI-MS, X-ray diffraction analysis, and CD method.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Diterpenes/isolation & purification , Euphorbia/chemistry , Triterpenes/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Three new pyrones, solanapyrones P-R (1-3), were afforded by the extracts of the endophytic fungus Alternaria tenuissima SP-07 isolated from the fresh root of Chinese herbal medicine Salvia przewalskii, along with the known solanapyrones (4-6) and benzopyrones (7-9). Solanapyrones P (1) and Q (2) possess an unprecedented nor-solanapyrone skeleton as natural products. Their structures were determined on the basis of NMR and HR-ESI-MS analysis. The plausible biosynthetic pathways to those unknown compounds were discussed. All the isolated compounds were evaluated for their antibacterial activities against six bacteria.
Subject(s)
Alternaria/chemistry , Anti-Bacterial Agents/chemistry , Pyrones/chemistry , Salvia/microbiology , Anti-Bacterial Agents/isolation & purification , Drugs, Chinese Herbal , Microbial Sensitivity Tests , Molecular Structure , Plant Roots/microbiology , Pyrones/isolation & purificationABSTRACT
From the twigs and leaves of Pseuduvaria indochinensis Merr., a new benzopyran derivative, pseudindochin (1), was isolated together with three known compounds, oligandrol (2), (6E,10E)-isopolycerasoidol (3) and polycerasoidol (4). The structure of compound 1 was elucidated on the basis of extensive spectroscopic data interpretation, including 1D, 2D NMR, HR-ESI-MS, UV and IR. Moreover, compounds 1-4 were evaluated in vitro for their cytotoxic activities against HL-60 and SMMC-7721 cell lines, but these compounds were essentially non-cytotoxic (IC50>30 µg/mL).
Subject(s)
Annonaceae/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Benzopyrans/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Benzopyrans/chemistry , Benzopyrans/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , HL-60 Cells , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Leaves/chemistryABSTRACT
AIMS: Kushecarpin D (KD) is a novel flavonoid isolated from the traditional Chinese herbal medicine Kushen (the dried root of Sophora flavescens Ait). As part of our continuous effort to explore Chinese traditional medicinal herbs and to identify novel natural anticancer products, the antiangiogenic properties of KD were examined in vitro using a human umbilical vein endothelial cell line (ECV304). MAIN METHODS: The SRB and Trypan Blue exclusion assays were used to evaluate the effect of KD on cell proliferation. The antiangiogenic activities of KD were evaluated through studies of cell migration, cell adhesion, and tube formation. DCFH-DA and DHE fluorescent assays were used to detect the reactive oxygen species (ROS) levels. Catalase activity was detected using the colorimetric ammonium molybdate method. Cell cycle and apoptosis were measured using flow cytometry and the Hoechst 33258 staining assay. KEY FINDINGS: The results indicated that KD showed antiangiogenic activity via inhibitory effects on cell proliferation, cell migration, cell adhesion, and tube formation. ROS levels were down-regulated and catalase activity was up-regulated after treatment with KD. The cell cycle was arrested at the G2/M phase, while no apoptosis was observed using the Hoechst 33258 staining assay or following the flow cytometric analysis of the sub-G1 proportion. SIGNIFICANCE: The antiangiogenic properties of KD, in combination with its anti-proliferative effect and ability to induce cell cycle arrest without inducing apoptosis, make it a good candidate for development as antitumor agent. However, further studies are essential to elucidate its mechanism of action.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Benzofurans/pharmacology , Benzopyrans/pharmacology , Sophora/chemistry , Angiogenesis Inhibitors/isolation & purification , Apoptosis/drug effects , Benzofurans/isolation & purification , Benzopyrans/isolation & purification , Catalase/metabolism , Cell Adhesion/drug effects , Cell Cycle/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , Flavonoids/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Plant Roots/chemistry , Reactive Oxygen Species/metabolismABSTRACT
Kushen, the dried root of Sophora flavescens Ait, is a traditional Chinese herbal medicine. Kushen alkaloids have been developed in China as anticancer drugs, and more potent antitumor activities have been identified in kushen flavonoids than in kushen alkaloids. In this study, the anti-angiogenic properties of (2S)-7,2',4'-triihydroxy-5-methoxy-8-dimethylallyl flavanone (Compound 1, a novel flavonoid isolated from Kushen), were examined using the human umbilical vein endothelial cell line (ECV304) in vitro. The results indicated that compound 1 shows anti-angiogenesis activity via inhibitory effects on cell proliferation, cell migration, cell adhesion, and tube formation. Further studies indicated that compound 1 blocks cell cycles in the G0/G1 phase without inducing apoptosis, and down regulates vascular endothelial growth factor (VEGF) expression. The free radical scavenging activity of compound 1 was found through 2',7'-dichlorofluorescin diacetate (DCFH-DA) incubation assay in cells. The anti-angiogenic properties of compound 1 and its antiproliferative effect on endothelial cells without causing apoptosis make it a good candidate for development as a agent against development of tumors.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Flavonoids/pharmacology , G1 Phase/drug effects , Resting Phase, Cell Cycle/drug effects , Sophora/chemistry , Vascular Endothelial Growth Factor A/biosynthesis , Antioxidants/pharmacology , Cell Adhesion/drug effects , Cell Cycle/drug effects , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Drugs, Chinese Herbal , Endothelial Cells/drug effects , Flavonoids/isolation & purification , Humans , Microtubules/drug effects , Plant Roots/chemistry , Reactive Oxygen Species/metabolismABSTRACT
Ten new tirucallane-type triterpenoids, represented by a rearranged skeleton dysolenticin A (1), dysolenticin B (2), a rare trinortriterpenoid dysolenticin C (3), three tirucallane triterpenoid derivatives with a hemiketal moiety dysolenticins D-F (4-6), dysolenticins G-I (7, 9, 10), and the new alkaloid dysolenticin J (12), together with seven known analogues were isolated from the twigs and leaves of Dysoxylum lenticellatum. Their structures were elucidated by extensive spectroscopic methods, and those of compounds 1, 3, 4, 6, and 10 were confirmed by single-crystal X-ray diffraction experiments. Dysolenticin J (12) showed significant vasodilative effects on intact rat aortic rings with a diastolic degree of 87.4% at 10 µg/mL.
Subject(s)
Alkaloids/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Meliaceae/chemistry , Triterpenes/isolation & purification , Vasodilator Agents/isolation & purification , Alkaloids/chemistry , Alkaloids/pharmacology , Animals , Aorta/drug effects , Crystallography, X-Ray , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Molecular Structure , Plant Stems/chemistry , Rats , Triterpenes/chemistry , Triterpenes/pharmacology , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacologyABSTRACT
Extraction of roots of Patrinia rupestris (Pall.) Juss. gave a new iridoid compound, 1ß,3α-diethyloxy-7-hydromethyl-4-(3-methyl-butyryloxymethyl)-cyclopenta-4(4a),7(7a)-diene[c]pyran-6-one (1), together with a known compound, (1α,4aα, 6α,7ß,7aα)-[4a,5,6,7,7a-hexahydro-6,7-dihydroxy-1-(3-methyl-1-oxobutoxy) cyclopenta[c]pyran-4,7-diyl]bis(methylene) 3-methyl-butanoic acid ester (2). The structure of 1 was characterised by HRESIMS, IR, UV, 1-D NMR and 2-D NMR methods. Compound 2 was isolated from this genus for the first time.
Subject(s)
Iridoids/isolation & purification , Patrinia/chemistry , Plant Extracts/isolation & purification , Plant Roots/chemistry , Iridoids/analysis , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/analysis , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
A dimeric eremophilane sesquiterpene lactone with a cyclobutane ring, biliguhodgsonolide (1) and an uncommon seco-sesquiterpene derivative, (4S,5S,6R,10R)-8,9-seco-12-hydroxyeremophil-7(11)-en-14,6;12,8-diolid-9-al (2), were isolated from the roots and rhizomes of Ligularia hodgsonii Hook. Their structures, including the absolute stereochemistry, were elucidated by spectroscopic data and CD analysis. The cyclobutane ring was confirmed by single-crystal X-ray diffraction.
Subject(s)
Asteraceae/chemistry , Lactones/chemistry , Naphthalenes/chemistry , Sesquiterpenes/chemistry , Crystallography, X-Ray , Lactones/isolation & purification , Models, Molecular , Molecular Conformation , Naphthalenes/isolation & purification , Plant Roots/chemistry , Polycyclic Sesquiterpenes , Rhizome/chemistry , Sesquiterpenes/isolation & purification , StereoisomerismABSTRACT
A novel dimeric secoiridoid glucoside, gentimacroside (1), and six known compounds (2-7) were isolated from the roots of Gentiana macrophylla Pall. Their structures were established on the basis of spectroscopic analysis, especially by means of 1D-, 2D-NMR and HRESIMS analyses.
Subject(s)
Gentiana/chemistry , Glucosides/isolation & purification , Iridoids/isolation & purification , Glucosides/chemistry , Iridoids/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Optical Rotation , Plant Roots/chemistry , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform InfraredABSTRACT
Although the quinolizidine alkaloids and flavonoids, the main active components of the traditional Chinese medicine Sophora flavescens, have been largely investigated, a new matrine alkaloid derivative 9alpha-hydroxy-7,11-dehydromatrine (1) and a rare 1,4-diazaindan-type alkaloid flavascensine (17), together with 15 known alkaloids, were isolated from S. flavescens. The structures were established on the basis of spectroscopic techniques.
Subject(s)
Alkaloids/isolation & purification , Quinolizidines/isolation & purification , Sophora/chemistry , Alkaloids/chemistry , Drugs, Chinese Herbal/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Molecular Structure , Plants, Medicinal/chemistry , Quinolizidines/chemistryABSTRACT
A novel trinorguaiane-type sesquiterpene named radicol (1), together with a known sesquiterpene dictamnol (2), was isolated from the petroleum ether-EtOAc-MeOH extracts of the root of Dictamnus radicis Cortex. The structure of 1 was elucidated as 1 alpha,5 alpha-dimethyl-4 alpha,10 alpha-bicyclo[3.5.0]dec-8-en-1 beta,5 beta-diol (1) on the basis of IR, HRESIMS, 1H and 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY.