ABSTRACT
Two new quinone derivatives, epoxyquinophomopsins A (1) and B (2), were purified from the EtOAc extract of endophytic fungus Phomopsis sp isolated from Morus cathayana. The structures of both compounds were determined based on 1D and 2D NMR and mass spectral data, as well as by x-ray diffraction analysis for 1. Compounds 1 and 2 were screened against eight receptor- (RTKs) and eight non-receptor tyrosine kinases (nRTKs). Both compounds showed strong inhibitory properties against Bruton's Tyrosine Kinase (nRTK) with their kinase activity were 19% and 20%, respectively. Only compound 1 that showed strong inhibitory properties against RTKs EGFR and HER-4 with its kinase activity were 16 and 15%, respectively. Thus, both compounds have potential as tyrosine kinase inhibitors.
Subject(s)
Phomopsis/chemistry , Protein-Tyrosine Kinases/drug effects , Molecular StructureABSTRACT
Amyloid ß (Aß) aggregation plays an essential role in promoting the progression of Alzheimer's disease (AD). Therefore, the inhibition of Aß aggregation is a potential therapeutic approach for AD. Herein, twenty-seven biflavonoids with different inter-flavonyl linkages and methoxy substitution patterns were isolated from several plants, and their Aß40 aggregation inhibitory activity was evaluated by the thioflavin-T fluorescence assay. Amentoflavone (1) and its monomethoxy derivatives (2, 3, and 5) exhibited the most potent inhibitory activity, with IC50 values of approximately 5⯵M. It was clarified that increasing the number of methoxy substituents on the biflavonoid structures attenuated the inhibitory activity. Moreover, the linkage and the methoxy substitution pattern had a marked influence on the inhibitory activity. Our investigation strongly supports that biflavonoids can be considered a new type of anti-Alzheimer agents that may be successfully developed for AD patients.
Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/antagonists & inhibitors , Biflavonoids/chemistry , Alzheimer Disease/pathology , HumansABSTRACT
A new farnesylated flavonol (4'-O-methylmacagigantin) and a new geranylated stilbene (macatrichocarpin H), together with eight known phenolic compounds, have been isolated from the leaves of Macaranga trichocarpa. Structures of these compounds were determined based on NMR and mass spectrroscopic data. Cytotoxic properties of the isolated compounds were tested against P-388 cells showing that mactrichocarpin G was the most active compound with IC50 was 3.5µM.
Subject(s)
Euphorbiaceae/chemistry , Flavonols/chemistry , Stilbenes/chemistry , Animals , Cell Line, Tumor , Flavonols/isolation & purification , Indonesia , Mice , Molecular Structure , Plant Leaves/chemistry , Stilbenes/isolation & purificationABSTRACT
A major hallmark of Alzheimer's disease is the cerebral accumulation and resulting cytotoxicity of amyloid-ß peptides, particularly Aß42. In this study, we used an MTT assay to investigate the inhibitory activity of biflavonoids 1-22 against Aß42 cytotoxicity in PC-12 cell cultures. Cytoprotective effects were observed for the following amentoflavone type biflavonoids: podocarpusflavone B 8, isoginkgetin 10, sciadopitysin 13, and kayaflavone 15. These biflavonoids exhibited strong activity in tested compounds, with EC50 values of 5.18, 10.77, 9.84, and 5.29 µM, respectively. Cell viability tests of PC-12 cells revealed that biflavonoids 13 and 15 had stronger inhibitory activities than apigenin 23 and (-)-epigallocatechin gallate 24.
Subject(s)
Amyloid beta-Peptides/toxicity , Biflavonoids/chemistry , Biflavonoids/pharmacology , Cell Survival/drug effects , Peptide Fragments/toxicity , Protective Agents/chemistry , Protective Agents/pharmacology , Animals , PC12 Cells , Rats , Structure-Activity RelationshipABSTRACT
Two new dihydroflavonol derivatives, macarecurvatins A and B, have been isolated from the leaves of Macaranga recurvata (Euphorbiaceaae), along with the known compounds diisoprenylaromadendrin, glyasperin A and broussoflavonol F. The structures of the new compounds were determined on the basis of spectroscopic evidence. Upon cytotoxic evaluation against P-388 cells, macarecurvatin B showed strong activity with an IC50 of 0.83 microM.
Subject(s)
Euphorbiaceae/chemistry , Flavonols/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Flavonols/isolation & purification , Flavonols/pharmacology , Leukemia P388/drug therapy , Magnetic Resonance Spectroscopy , Mice , Plant Leaves/chemistry , Spectrophotometry, UltravioletABSTRACT
Two geranylated and methylated flavonol derivatives, macarhizinoidins A (1) and B (2), along with a known phenolic compound methyl 4-isoprenyloxycinnamate (3), have been isolated from the methanol extract of the leaves M. rhizinoides. The structures of these compounds were identified based on their spectroscopic data. On cytotoxic evaluation against murine leukemia P-388 cells, compounds 1-2 showed IC50 values of 11.4 and 13.9 microM, respectively, while compound 3 was inactive.
Subject(s)
Euphorbiaceae/chemistry , Flavonols/isolation & purification , Animals , Flavonols/chemistry , Flavonols/pharmacology , Leukemia P388/drug therapy , Leukemia P388/pathology , Mice , Plant Extracts/analysisABSTRACT
Here, we describe amentoflavone-type biflavonoids, which were isolated from natural sources and were found to inhibit beta-secretase (BACE-1). The structure-activity relationship was studied, and compounds 1-8, 10, 17, and 18 showed BACE-1 inhibitory activity. Among these compounds, 2,3-dihydroamentoflavone 17 and 2,3-dihydro-6-methylginkgetin 18 exhibited potent inhibitory effects with IC(50) values of 0.75 and 0.35 microM, respectively.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Biflavonoids/chemistry , Protease Inhibitors/chemistry , Amyloid Precursor Protein Secretases/metabolism , Biflavonoids/pharmacology , Protease Inhibitors/pharmacology , Structure-Activity RelationshipABSTRACT
Two chalcone derivatives, 2'-hydroxychalcone (1) and desmethylinfectocaryone (2), together with five known phenolic compounds infectocaryone (3), cryptocaryone (4), kurzichalcolactone A (5), pinocembrin (6) and trans-N-feruloyltyramine (7), were isolated from the methanol extract of the wood of Cryptocarya konishii. The structures of the new compounds were determined based on the analysis of spectroscopic data, including UV, IR, 1D and 2D NMR, and mass spectra. Evaluation of the cytotoxic and tyrosine kinase inhibitory activities of compounds 1-7 showed that compounds 2-4 strongly inhibited the growth of murine leukemia P-388 cells, whereas compound 4 significantly inhibited the enzyme.
Subject(s)
Cryptocarya , Cytotoxins/toxicity , Phenols/toxicity , Plant Extracts/toxicity , Protein Kinase Inhibitors/toxicity , Protein-Tyrosine Kinases/antagonists & inhibitors , Cytotoxins/chemistry , Cytotoxins/isolation & purification , Endothelium, Vascular/drug effects , Endothelium, Vascular/enzymology , Humans , Phenols/chemistry , Phenols/isolation & purification , Plant Bark , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/isolation & purification , Protein-Tyrosine Kinases/metabolismABSTRACT
New prenylated flavones, artoindonesianins Z-4 and Z-5, together with four known prenylated flavones, artonin E, 12-hydroxyartonin E, artobiloxanthone, and cycloartobiloxanthone, have been isolated from the methanol extract of the tree bark of Artocarpus lanceifolius. The structures of these compounds were determined on the basis of spectroscopic data, including UV, IR, 1D and 2D NMR, and mass spectra. The cytotoxic effect of the isolated compounds against murine leukemia P-388 cells is described.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Artocarpus/chemistry , Flavones/chemistry , Flavones/pharmacology , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Flavones/isolation & purification , Leukemia P388/drug therapy , Magnetic Resonance Spectroscopy , Mass Spectrometry , Methanol , Mice , Plant Bark/chemistry , Prenylation , Solvents , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform InfraredABSTRACT
A new 2-arylbenzofuran derivative (diptoindonesin G) (1), along with nine known oligostilbenes, have been isolated and identified from the acetone extract of the tree bark of Hopea mengarawan. The structures of these compounds were determined based on spectroscopic data, including 2D NMR and HREIMS spectra. On cytotoxic evaluation of the isolated compounds against murin leukemia P-388 cells, compound 1 was the strongest in inhibiting the growth of the cells.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Benzofurans/chemistry , Benzofurans/pharmacology , Dipterocarpaceae/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Benzofurans/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Leukemia P388/drug therapy , Magnetic Resonance Spectroscopy , Mice , Plant Bark/chemistry , Solvents , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform InfraredABSTRACT
A new oligostilbenoid, diptoindonesin C, has been isolated from the tree bark of Shorea pinanga Scheff., along with the two known oligostilbenoids gnetin H and hopeaphenol, and a known coumarin scopoletin. The new oligostilbenoid was moderately active against brine shrimps Artemia salina.
Subject(s)
Dipterocarpaceae/chemistry , Plant Bark/chemistry , Plant Extracts/isolation & purification , Stilbenes/isolation & purification , Molecular Structure , Phenols , Stilbenes/analysis , Stilbenes/chemistryABSTRACT
Two isoprenylated flavanones, macatrichocarpins A and B, and two isoprenylated dihydrochalcones, macatrichocarpins C and D, have been isolated and identified from the acetone extract of the leaves of Macaranga trichocarpa. The structures of these compounds were determined based on spectroscopic data, including UV, IR, 1D and 2D NMR spectroscopic and HREIMS data. This is the first report of the presence of dihydrochalcone derivatives in the genus Macaranga.
Subject(s)
Chalcones/chemistry , Euphorbiaceae/chemistry , Flavones/chemistry , Molecular StructureABSTRACT
A new oxepinoflavone, artoindonesianin E1 (1), was isolated from the wood of Artocarpus elasticus, along with four known prenylated flavones: artocarpin (2), cycloartocarpin (3), cudraflavones A (4) and C (5). The structure of the new compound was identified by spectroscopic methods. Upon cytotoxic evaluation against murine leukemia P-388 cells, the new compound showed IC(50) 5.0 microg/mL.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Artocarpus/chemistry , Flavones/pharmacology , Flavonoids/pharmacology , Oxepins/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Survival/drug effects , Flavones/chemistry , Flavones/isolation & purification , Flavonoids/chemistry , Flavonoids/isolation & purification , Inhibitory Concentration 50 , Mice , Molecular Structure , Oxepins/chemistry , Oxepins/isolation & purificationABSTRACT
A new farnesylated flavonol derivative, macagigantin (1), together with two known flavonoids, glyasperin A (2) and apigenin (3), had been isolated from the acetone extract of the leaves of Macaranga gigantea. The structure of the new compound was elucidated as 6-farnesylkaempferol based on its spectroscopic data, including UV, IR, 1D and 2D NMR, and HR-EI-MS spectra. Compounds 1-3 were evaluated for their cytotoxic properties against P-388 cells, their IC(50) values being 11.3, 6.0, and 5.1 microM, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Euphorbiaceae/chemistry , Flavonols/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Flavonols/chemistry , Flavonols/pharmacology , Indonesia , Leukemia P388 , Mice , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Leaves/chemistry , Structure-Activity RelationshipABSTRACT
A new methylated flavonol, 5,7,2',4'-tetrahydroxy-3-methoxyflavone (1), had been isolated from the methanol extract of the wood of Morus australis, along with nine known compounds, kuwanon C (2), morusin (3), morachalcone A (4), oxyresveratrol (5), 4'-(2-methyl-2-buten-4-yl)oxyresveratrol (6), moracins M (7) and C (8), alboctalol (9), and macrourin B (10). The structures of these compounds were determined based on spectral evidence, including UV, IR, NMR, and mass spectra. Cytotoxic properties of compounds 1-10 were evaluated against murine leukemia P-388 cells. The prenylated stilbene 6 and 2-arylbenzofuran 8, and morusin (3) were found to have strong cytotoxic effects with IC50 values of 6.9, 8.7, and 10.1 microM, respectively.
Subject(s)
Flavonols/chemistry , Morus/chemistry , Phenols/chemistry , Wood , Flavones/chemistry , Flavones/isolation & purification , Flavonols/isolation & purification , Magnetic Resonance Spectroscopy , Models, Molecular , Phenols/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , SpectrophotometryABSTRACT
A new oligostilbenoid derivative, diptoindonesin F (1), along with five known oligostilbenoids, (-)-ampelopsin A (2), (-)-alpha-viniferin (3), ampelopsin E (4), (-)-vaticanol B (5), and (-)-hemsleyanol D (6), were isolated from the methanol extract of the tree bark of Shorea gibbosa. The structure of the new compound was determined based on the analysis of spectroscopic data, including UV, IR, NMR 1-D and 2-D, and mass spectra. Cytotoxic properties of the isolated oligostilbenoids were evaluated against murine leukemia P-388 cells with the result that compounds 2 and 4 showed the highest cytotoxicity.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Dipterocarpaceae/chemistry , Stilbenes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Leukemia P388 , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Stilbenes/chemistry , Stilbenes/isolation & purification , Structure-Activity RelationshipABSTRACT
A new resveratrol tetramer, named diptoindonesin E, was isolated from the acetone extract of the tree bark of Dipterocarpus hasseltii, together with five known resveratrol oligomers (-)-epsilon-viniferin, laevifonol, (-)-alpha-viniferin, vaticanol B, (-)-hopeaphenol, and a coumarin, scopoletin. The structures of these compounds were determined from spectroscopic evidence. Cytotoxicity test of the isolated compounds showed that hopeaphenol strongly inhibited murine leukemia P-388 cells.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Ericales , Phytotherapy , Plant Extracts/pharmacology , Stilbenes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor/drug effects , Mice , Plant Bark , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Resveratrol , Stilbenes/administration & dosage , Stilbenes/chemistry , Stilbenes/therapeutic use , Structure-Activity RelationshipABSTRACT
A new flavanone, 7-hydroxy-5,6-dimethoxyflavanone (1), together with three other flavonoids, didymocarpin (2), 2',4'-dihydroxy-5',6'-dimethoxychalcone (3), and isodidymocarpin (4), had been isolated from the methanol extract of the tree bark of Cryptocarya costata. The structures of these compounds were determined based on spectral evidence, including UV, IR, 1-D and 2-D NMR, and mass spectra. Cytotoxic properties of compounds 1-4 were evaluated against murine leukemia P-388 cells. The chalcones 3 and 4 were found to have substantial cytotoxicity with IC50 of 5.7 and 11.1 microM, respectively.
Subject(s)
Chalcones/isolation & purification , Cryptocarya/chemistry , Flavanones/isolation & purification , Plant Stems/chemistry , Trees/chemistry , Animals , Cell Survival/drug effects , Chalcones/chemistry , Chalcones/toxicity , Flavanones/chemistry , Flavanones/toxicity , Leukemia P388 , Magnetic Resonance Spectroscopy , Mice , Models, MolecularABSTRACT
Several species of the genus Artocarpus (Moraceae) have been investigated in our laboratories during the last decade. Over 60 phenolic constituents have been discovered and characterized, including 27 new compounds from 13 Indonesian taxa of Artocarpus, namely A. champeden, A. lanceifolius, A. teysmanii, A. scortechinii, A. rotunda, A. maingayi, A. kemando, A. bracteata, A. altilis, A. fretessi, A. gomezianus, A. reticulatus and A. glaucus. The principal and the most pronounced features of these phenolic constituents are the assembly of an isoprenyl substituent at C-3 of a flavone skeleton by closure of an ether bridge or a carbon-carbon linkage with the B ring of the skeleton, which may further rearrange into xanthone to produce various classes of natural products. The structures of the new and unusual natural products are presented. Many of the metabolites also exhibit cytotoxic effect against murine leukemia P388 cells.
ABSTRACT
A new modified stilbene dimer, diptoindonesin D (1), was isolated from the acetone extract of the tree bark of Hopea dryobalanoides, together with seven known compounds, parviflorol (2), (-)-balanocarpol (3), heimiol A (4), hopeafuran (5), (+)-alpha-viniferin (6), vaticanol B (7) and (-)-hopeaphenol (8). Cytotoxic properties of compounds 1-8 were evaluated against murine leukemia P-388 cells. Compound 8 was found to be the most active with IC50 of 5.7 microM.