ABSTRACT
Three new meroterpenoids (1-3) and ten known ones (4-13) were obtained from the endophytic fungus Talaromyces primulinus H21 isolated from the plant of Euphorbia sikkimensis. Their structures including their absolute configurations were elucidated by extensive analysis of spectroscopic data such as HR-ESI-MS, 1D/2D NMR, and X-ray diffraction of single crystal together with comparison of experimental ECD with calculated ECD. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 3, 9, 12, and 13 exhibited certain inhibition on NO production, with IC50 values of 27.19, 41.55, 25.23, and 24.71 µM, respectively.
Subject(s)
Nitric Oxide , Talaromyces , Terpenes , Talaromyces/chemistry , Mice , Molecular Structure , Nitric Oxide/metabolism , Animals , Terpenes/isolation & purification , Terpenes/pharmacology , RAW 264.7 Cells , Endophytes/chemistry , ChinaABSTRACT
Four new cytochalasans, arbuschalasins A-D (1-4), along with thirteen known analogues (5-17), were isolated from the solid rice medium of endophytic fungus Xylaria arbuscula. Arbuschalasins A-B feature a rare 5/6/6/6 fused ring system while arbuschalasin D was characterized as the first example of natural cytochalasans that possesses a 5/5/11 fused scaffold. The structures of 1-4 were assigned by spectroscopic data, with their absolute structures being determined by electronic circular dichroism (ECD) calculations. All of the isolates were evaluated against the human colorectal adenocarcinoma cell lines (HCT15). Compounds 6 and 7 showed significant inhibitory effects (IC50 values were 13.5 and 13.4 µM, respectively), being more active than those of the positive control, fluorouracil (103.1 µM).
Subject(s)
Ascomycota/chemistry , Cytochalasins/isolation & purification , Rhizophoraceae/microbiology , Cell Line, Tumor , Cell Survival , Cytochalasins/chemistry , Fermentation , Humans , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
The first and asymmetric total synthesis of 4ß-acetoxyprobotryane-9ß,15α-diol, containing a rare and highly strained trans-fused bicyclo[3.3.0]octane ring system, has been achieved. The synthetically challenging [6-5-5] tricyclic ring system in the final product was efficiently and diastereoselectively synthesized via an asymmetric rhodium-catalyzed [4 + 2] cycloaddition reaction, followed by a unique benzilic acid type rearrangement under very mild conditions. The seven contiguous stereocenters were installed efficiently and diastereoselectively.
ABSTRACT
The phytochemical study of Euphorbia prolifera led to the isolation of two tiglianes (1 and 2) and 23 mysrinanes (3-25). Most of these isolates showed significant antiadipogenic activity in 3T3-L1 adipocyte without apparent cytotoxicity. Subsequent structural modification yielded 10 derivatives, among which 1a, the 5- O-acetyl derivative of 1, turned out to be the most active compound with improved triglyceride-lowering activity (EC50 for 1 and 1a: 0.61 and 0.32 µM, respectively) and reduced cytotoxicity (selectivity index for 1 and 1a: 28 and 312, respectively). The structure-activity relationship study revealed that the trans-fused 5/7/6 ring system in an angular shape was important to the activity. A mechanistic study indicated that 1 and 1a could inhibit the glucocorticoid receptor α-Dexras1 axis in adipocyte, leading to the retardation of cell differentiation at the early stage. These findings may provide a new type of lipid-lowering agents for future antiobesity drug development.
Subject(s)
Adipogenesis/drug effects , Anti-Obesity Agents/pharmacology , Phorbols/pharmacology , Receptors, Glucocorticoid/antagonists & inhibitors , ras Proteins/metabolism , 3T3-L1 Cells , Adipocytes , Animals , Anti-Obesity Agents/chemical synthesis , Anti-Obesity Agents/isolation & purification , Down-Regulation , Euphorbia/chemistry , Mice , Molecular Docking Simulation , Molecular Structure , Phorbols/chemical synthesis , Phorbols/isolation & purification , Receptors, Glucocorticoid/metabolism , Structure-Activity Relationship , ras Proteins/geneticsABSTRACT
Acetaminophen (APAP) overdose-induced hepatotoxicity is tightly associated with oxidative stress. Tetrahydrocurcumin (THC) and octahydrocurcumin (OHC), the primary and final hydrogenated metabolites of curcumin (CUR), possess stronger antioxidant activity in vitro. The present study was performed to investigate the potential and mechanism of OHC and THC against APAP-induced hepatotoxicity in parallel to CUR. Our results showed that OHC and THC dose-dependently enhanced liver function (ALT and AST levels) and alleviated histopathological deterioration. Besides, OHC and THC significantly restored the hepatic antioxidant status by miring level of MDA and ROS, and elevated levels of GSH, SOD, CAT and T-AOC. In addition, OHC and THC markedly suppressed the activity and expressions of CYP2E1, and bound to the active sites of CYP2E1. Moreover, OHC and THC activated the Keap1-Nrf2 pathway and enormously enhanced the translational activation of Nrf2-targeted gene (GCLC, GCLM, NQO1 and HO-1) against oxidative stress, via inhibiting the expression of Keap1 and blocking the interaction between Keap1 and Nrf2. Particularly, OHC and THC exerted superior hepato-protective and antioxidant activities to CUR. In conclusion, OHC and THC possess favorable hepato-protective effect through restoring antioxidant status, inhibiting CYP2E1 and activating Keap1-Nrf2 pathway, which might represent promising antioxidants for the treatment of APAP-induced hepatotoxicity.
Subject(s)
Acetaminophen/adverse effects , Chemical and Drug Induced Liver Injury/prevention & control , Curcumin/administration & dosage , Cytochrome P-450 CYP2E1/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Protective Agents/administration & dosage , Animals , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/metabolism , Curcumin/analogs & derivatives , Curcumin/chemistry , Curcumin/metabolism , Cytochrome P-450 CYP2E1/genetics , Humans , Hydrogenation , Kelch-Like ECH-Associated Protein 1/genetics , Liver/drug effects , Liver/metabolism , Male , Mice , NF-E2-Related Factor 2/genetics , Oxidative Stress/drug effects , Protective Agents/chemistry , Protective Agents/metabolism , Signal Transduction/drug effectsABSTRACT
Three new thiodiketopiperazines, geospallins Aâ»C (1â»3), together with nine known analogues (4â»12), were isolated from the culture of the deep-sea sediment-derived fungus Geosmithia pallida FS140. Among them, geospallins A and B (1 and 2) represent rare examples of thiodiketopiperazines featuring an S-methyl group at C-10 and a tertiary hydroxyl group at C-11. Their structures were determined by high-resolution electrospray mass spectrometry (HRESIMS), spectroscopic analyses, and electronic circular dichroism (ECD) calculations. Their angiotensin-converting enzyme (ACE) inhibitory activity was reported, and geospallins Aâ»C (1â»3) showed inhibitory activity with IC50 values of 29â»35 µM.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Aquatic Organisms/chemistry , Hypocreales/chemistry , Peptidyl-Dipeptidase A/chemistry , Piperazines/pharmacology , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/isolation & purification , Circular Dichroism , Enzyme Assays/methods , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Piperazines/chemistry , Piperazines/isolation & purification , Spectrometry, Mass, Electrospray IonizationABSTRACT
The secondary metabolites of endophytic fungus Cerrena sp.A593 from Pogostemon cablin and their cytotoxic activities were investigated. Eight sesquiterpenoids were isolated from the fermentation broth of the strain A593 by silica gel, reverse phase silica gel, Sephadex LH-20, HPLC and so on. Their structures were identified as chloriolin B(1), chloriolin C(2), pleurocybellone A(3), dihydrohypnophilin(4), cucumin F(5), antrodin A(6), 10α-hydroxyamorphan-4-en-3-one(7), and connatusin A(8). Compounds 1- 8 were firstly found from the genus Cerrena. All isolated sesquiterpenoids were evaluated for in vitro cytotoxic activities against HepG-2, SF-268, MCF-7 and NCI-H460 tumor cell lines. Compounds 1-3 showed inhibitory activities against the four tumor cell lines with IC50 values ranging from 20.33 to 63.13 µmolâ¢L⻹.
Subject(s)
Antineoplastic Agents/isolation & purification , Pogostemon/microbiology , Polyporales/chemistry , Sesquiterpenes/isolation & purification , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Endophytes/chemistry , Humans , Sesquiterpenes/pharmacologyABSTRACT
Two new compounds isobenzofuranone A (1) and indandione B (2), together with eleven known compounds (3-13) were isolated from liquid cultures of an endophytic fungus Alternaria sp., which was obtained from the medicinal plant Morinda officinalis. Among them, the indandione (2) showed a rarely occurring indanone skeleton in natural products. Their structures were elucidated mainly on the basis of extensive spectroscopic data analysis. All of the compounds were evaluated with cytotoxic and α-glucosidase inhibitory activity assays. Compounds 11 and 12 showed significant inhibitory activities against four tumor cell lines; MCF-7, HepG-2, NCI-H460 and SF-268, with IC50 values in the range of 1.91-9.67 µM, and compounds 4, 5, 9, 10, 12 and 13 showed excellent inhibitory activities against α-glucosidase with IC50 values in the range of 12.05-166.13 µM.
Subject(s)
Alternaria , Furans , Indans , Morinda/microbiology , Alternaria/isolation & purification , Alternaria/metabolism , Furans/analysis , Furans/chemistry , Furans/metabolism , Indans/analysis , Indans/chemistry , Indans/metabolismABSTRACT
Phytochemical investigation on the herbs of Lycopodium japonicum led to the isolation of a new serratene triterpenoid, 3α,21α-dihydroxy-16-oxoserrat-14-en-24-yl p-coumarate (1), together with two known ones, lycernuic ketone C (2) and tohogenol (3). Their structures were elucidated by extensive spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MS. The 13C NMR data of tohogenol was first reported.
Subject(s)
Drugs, Chinese Herbal/isolation & purification , Lycopodium/chemistry , Triterpenes/isolation & purification , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Inhibitory Concentration 50 , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Eutypellol A (1), the first norsesquiterpenoid of sequicarene family, as well as eutypellol B (2), a rare 7-methyl oxidized 2-carene derivative, and one new natural product 2-(2-hydroxy-4-methylcyclohex-3-enyl)propanoic acid (3), along with eight known terpenoids, were isolated from the marine sediment-derived fungus Eutypella scoparia FS46 collected from the South China Sea. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 1-3 were evaluated for their antibacterial activities against Staphylococcus aureus and cytotoxic activities against MCF-7, NCI-H460, and SF-268 tumor cell lines.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Monoterpenes/isolation & purification , Sesquiterpenes/isolation & purification , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Drug Screening Assays, Antitumor , Geologic Sediments , Humans , Marine Biology , Microbial Sensitivity Tests , Molecular Structure , Monoterpenes/chemistry , Monoterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Staphylococcus aureus/drug effectsABSTRACT
Cytosporaphenones A-C, one new polyhydric benzophenone and two new naphtopyrone derivatives, along with eight known ones, were isolated from Cytospora rhizophorae, an endophytic fungus from Morinda officinalis. Their structures were fully characterized by means of detailed spectroscopic analysis and X-ray single crystal diffraction. To our knowledge, the three new compounds were the most highly oxygenated metabolites of their families discovered in nature. Moreover, all of the compounds were evaluated for in vitro cytotoxic activities against MCF-7, NCI-H460, HepG-2 and SF-268 tumor cell lines, and the new compound 1 exhibited weak growth inhibitory activity against the tumor cell lines MCF-7 and HepG-2 with IC50 values of 70 and 60µM, respectively.
Subject(s)
Antineoplastic Agents/chemistry , Ascomycota/chemistry , Phenols/chemistry , Antineoplastic Agents/isolation & purification , Benzophenones/chemistry , Benzophenones/isolation & purification , Cell Line, Tumor , Endophytes/chemistry , Humans , Molecular Structure , Morinda/microbiology , Naphthalenes/chemistry , Naphthalenes/isolation & purification , Phenols/isolation & purification , Pyrones/chemistry , Pyrones/isolation & purificationABSTRACT
Three new diketopiperazines, dichotocejpins A-C (1-3), together with eight known analogues (4-11), were isolated from the culture of the deep-sea sediment derived fungus Dichotomomyces cejpii FS110. Their structures, including absolute configurations, were elucidated by a combination of HRESIMS, NMR, X-ray crystallography, and ECD calculations. Compounds 4-6, 10-11 showed significant cytotoxic activities against MCF-7, NCI-H460, HepG-2, and SF-268 tumor cell lines. Compound 1 exhibited excellent inhibitory activity against α-glucosidase with an IC50 of 138 µM.
Subject(s)
Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Fungi/chemistry , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Fermentation , Geologic Sediments/microbiology , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Spectrometry, Mass, Electrospray Ionization , alpha-Glucosidases/metabolismABSTRACT
Two new secondary metabolites, endomeketals A-B (1-2), a new natural product (3), and a known compound (4) were isolated from the ethyl acetate extract of the endophytic fungus Endomelanconiopsis endophytica A326 derived from Ficus hirta. Their structures were determined on the basis of extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. However, no compound showed cytotoxic activity against these human tumor cell lines.
Subject(s)
Ascomycota/chemistry , Biological Products/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Ascomycota/metabolism , Biological Products/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Endophytes , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Secondary MetabolismABSTRACT
Chemical examination of the liquid culture of Endomelanconiopsis endophytica A326 isolated from the Chinese folk medicine Ficus hirta resulted in the isolation of two new xyloketals named xyloketals K and L (1-2) and three known analogs (3-5) including a new natural product (5). Their structures were determined on the basis of extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against the SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. Nonetheless, no significant activity was observed.
Subject(s)
Pyrans/isolation & purification , Ascomycota/chemistry , Drug Screening Assays, Antitumor , Ficus/chemistry , Hep G2 Cells , Humans , Molecular Structure , Plants, Medicinal/chemistry , Pyrans/chemistry , Pyrans/pharmacologyABSTRACT
Chemical investigation of the 90% acetone extract of the branches and leaves of Sabina gaussenii led to the isolation of two new cinnamyl isovalerate derivatives (1-2) and eighteen known compounds (3-20). Their structures were determined mainly by means of MS, 1D- and 2D-NMR data, and this is the first time these compounds have been reported from this plant. The biological activity test results indicated that the 90% acetone extract showed cytotoxicity against the human lung adenocarcinoma (A549) cell line (IC50 = 0.98 ± 0.1 µg/mL), compound 6 showed cytotoxicities against human cervical carcinoma (HeLa) (IC50 = 0.4 ± 0.1 µM ) and human gastric carcinoma (BGC-823) (IC50 = 0.9 ± 0.2 µM) cancer cell lines, and compound 19 showed cytotoxicities against HeLa (IC50 = 1.5 ± 0.4 µM), BGC-823 (IC50 = 7.0 ± 0.8 µM ), and A549 (IC50 = 10.6 ± 1.5 µM ) cancer cell lines.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Cinnamates/isolation & purification , Cupressaceae/chemistry , Plant Extracts/chemistry , Valerates/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , China , Cinnamates/chemistry , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Molecular Structure , Plant Leaves/chemistry , Valerates/chemistryABSTRACT
A pair of new azaphilone epimers, perangustols A-B (1-2), and two new natural products (3-4), together with two known metabolites (5-6) were isolated from the culture of the marine sediment-derived fungus Cladosporium perangustum FS62. The structures of these compounds were established on the basis of extensive spectroscopic analysis. The isolated compounds (1-6) were evaluated for their cytotoxic activities against the SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. Nonetheless, no significant activity was observed.
Subject(s)
Benzopyrans/chemistry , Benzopyrans/isolation & purification , Cladosporium/chemistry , Pigments, Biological/chemistry , Pigments, Biological/isolation & purification , Benzopyrans/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Geologic Sediments , Hep G2 Cells , Humans , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Pigments, Biological/pharmacologyABSTRACT
Chemical investigation on the soft coral Sarcophyton ehrenbergi collected from the Xisha Islands of the South China Sea have led to the isolation of eight cembranoids including five new ones, sarcophytonoxides A-E (1-5). The structures of new cembranoids (1-5) were determined by spectroscopic analysis and comparison of the NMR data with those of related analogues. The cytotoxicities of compounds 1-8 against human ovarian cancer cell line A2780 were also evaluated.
Subject(s)
Anthozoa/chemistry , Diterpenes/chemistry , Animals , Carbon-13 Magnetic Resonance Spectroscopy , Cell Line, Tumor , Cell Survival/drug effects , China , Diterpenes/pharmacology , Humans , Models, Molecular , Molecular Conformation , Proton Magnetic Resonance SpectroscopyABSTRACT
Chemical investigation of the liquid culture of the endophytic fungus Bipolaris sorokiniana A606, which was isolated from the medicinal plant Pogostemon cablin resulted in the isolation of four new cytotoxic compounds, named isocochlioquinones D-E (1-2) and cochlioquinones G-H (3-4), along with five known cochlioquinone analogues (5-9). Their structures were determined on the basis of extensive spectroscopic analysis. Isocochlioquinone D (1) possessed a rare benzothiazin-3-one moiety and cochlioquinone G (3) was the first example of cochlioquinones bearing an indole-4,7-dione fragment. All of the isolates (1-9) were evaluated for their cytotoxic activities against MCF-7, NCI-H460, SF-268 and HepG-2 tumor cell lines by the sulforhodamine B (SRB) assay. Compounds 4 and 6-9, featuring a cochlioquinone core, exhibited potent cytotoxicities in vitro against the four tumor cell lines, and a preliminary structure-activity relationship of these compounds was also discussed.
Subject(s)
Antineoplastic Agents/chemistry , Ascomycota/chemistry , Benzoquinones/chemistry , Indolequinones/chemistry , Lamiaceae/microbiology , Antineoplastic Agents/isolation & purification , Benzoquinones/isolation & purification , Cell Line, Tumor/drug effects , Humans , Indolequinones/isolation & purification , Molecular Structure , Structure-Activity RelationshipABSTRACT
A new cytotoxic roridin-type trichothecene macrolide named epiroridin acid (1) and two known compounds epiroridin E (2) and mytoxin B (3) were isolated from the liquid culture of Myrothecium roridum A553, which was isolated from the medicinal plant Pogostemon cablin. The structure of the new macrolide (1) was elucidated by extensive spectroscopic measurements (UV, IR, MS, and 1D and 2D NMR) analyses. All isolated compounds (1-3) were evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. The new compound (1) exhibited well cytotoxicity against the four selected tumor cell lines.
Subject(s)
Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Hypocreales/chemistry , Macrolides/isolation & purification , Macrolides/pharmacology , Trichothecenes/isolation & purification , Trichothecenes/pharmacology , Anti-Bacterial Agents , Antineoplastic Agents/chemistry , Cell Line, Tumor , Endophytes , Humans , Macrolides/chemistry , Molecular Structure , Trichothecenes/chemistryABSTRACT
To study active secondary metabolites of endophytic fungus Diaporthe longicolla A616 isolated from Pogostemon cablin. Ten compounds were isolated from fermentation product of the strain 616 by silica gel, reverse phase silica gel, Sephadex-LH20, HPLC and so on. Their structures were identified as 1,3-diamino-1,3-dimethylurea(1),(7R,9R)-7-hydroxy-9-propyl-5-nonen-9-olide(2), Ergosta-5,7,22-trien-3ß-ol(3),(22E,24R)-ergosta-4,6,8(14)-22-tetraen-3-one(4),(22E,24R)-3ß,5α-dihydroxy-6ß-ergosta-7,22-diene(5), citreoisocoumarin(6), glycerol monolinoleate(7), 1-(2-hydroxyethoxy)ethyl(E)-octadec-9-enoate(8), cyclo-(L-Pro-L-Ala)(9), cyclo(L)-Pro-(L)-Val(10), respectively, based on extensive spectroscopic analysis and literature comparisons. Compounds 6-10 were isolated from the genus Diaporthe for the first time. All isolated compounds were evaluated for in vitro cytotoxic activities against SF-268, MCF-7, NCI-H460 and HepG-2 tumor cell lines. Compounds 4 and 5 showed potent growth inhibitory activities against the four cell lines with IC50 values of 5.3, 6.5, 12.2, 6.1µmolâ¢L⻹ and 8.2, 5.2, 6.1, 9.4µmolâ¢L⻹, respectively.