RESUMO
Phytochemical study on the flowers of Hypericum formosanum Maxim. (Hypericaceae) led to the isolation of formohyperins G-L (1-6), whose structures were assigned by detailed spectroscopic analysis. Formohyperins G-L (1-6) are new benzoylphloroglucinols substituted by a C10 unit, a prenyl group, and a methyl group. Formohyperins G-J (1-4) possess a 6/6/6-tricyclic structure, while formohyperins K (5) and L (6) have a unique 6/6/5/4-tetracyclic structure consisting of cyclohexadienone, dihydropyrane, cyclopentane, and cyclobutane rings. The absolute configurations of 1-6 were deduced by analysis of the ECD spectra. Formohyperins G-J (1-4) and L (6) were found to show potent inhibitory activities against IL-1ß release from LPS-treated murine microglial cells with EC50 values of 5.0, 10.9, 6.3, 10.8, and 13.7 µM, respectively, without cytotoxicity. 6-O-Methylformohyperins G (1a) and I (3a) also exhibited the inhibitory activities with EC50 values of 4.7 and 2.7 µM, respectively, although they were cytotoxic against microglial cells.
Assuntos
Flores , Hypericum , Floroglucinol , Hypericum/química , Animais , Floroglucinol/química , Floroglucinol/farmacologia , Flores/química , Camundongos , Estrutura Molecular , Interleucina-1beta/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Prenilação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Lipopolissacarídeos/farmacologia , Linhagem CelularRESUMO
Formohyperins A-F, previously undescribed meroterpenes, and grandone, a prenylated benzoylphloroglucinol being considered to be one of their biogenetic precursors, were isolated from the flowers of a Hypericaceous plant, Hypericum formosanum Maxim. Detailed spectroscopic analyses showed that formohyperins A-D were meroterpenes with an enolized 3-phenylpropane-1,3-dione moiety. Formohyperins E and F were elucidated as meroterpenes having a 4-benzoyl-5-hydroxycyclopent-4-ene-1,3-dione moiety. Formohyperins A-C and E were optically active, and their absolute configurations were deduced by comparison of the experimental and TDDFT calculated ECD spectra. In contrast, formohyperin D was concluded to be a racemate. Formohyperins A-F and grandone were found to show inhibitory activities against LPS-stimulated IL-1ß production from murine microglial cells with EC50 values of 13.2, 6.6, 8.5, 24.3, 4.1, 10.9, and 3.0 µM, respectively.
Assuntos
Hypericum , Floroglucinol , Camundongos , Animais , Floroglucinol/farmacologia , Floroglucinol/química , Hypericum/química , Flores , Microglia , Prenilação , Estrutura MolecularRESUMO
Phytochemical study on the roots of a medicinal plant Ferula communis L. (Apiaceae) resulted in the isolation of 20 sesquiterpenes including 12 previously undescribed compounds, dauferulins A-L (1-12). The detailed spectroscopic analysis revealed 1-12 to be daucane-type sesquiterpenes with a p-methoxybenzoyloxy group at C-6. The absolute configurations of 1-12 were deduced by analysis of the ECD spectra. Dauferulins A-L (1-12), known sesquiterpenes (13-20), and analogues (14a-14l) derived from 6-O-p-methoxybenzoyl-10α-angeloyloxy-jeaschkeanadiol (14) were evaluated for their effects on AMPK phosphorylation in human hepatoma HepG2 cells as well as inhibitory activities against erastin-induced ferroptosis on human hepatoma Hep3B cells and IL-1ß production from LPS-treated murine microglial cells.
Assuntos
Carcinoma Hepatocelular , Ferula , Neoplasias Hepáticas , Sesquiterpenos , Humanos , Animais , Camundongos , Ferula/química , Carcinoma Hepatocelular/tratamento farmacológico , Estrutura Molecular , Sesquiterpenos/química , Raízes de Plantas/químicaRESUMO
Phytochemical study on the whole plants of a Gentianaceous medicinal plant, Canscora lucidissima, gave one new acylated iridoid glucoside, canscorin A (1), and two new xanthone glycosides (2 and 3) together with 17 known compounds including five xanthones, eight xanthone glycosides, two benzophenone glucosides, caffeic acid, and loganic acid. Canscorin A (1) was assigned as a loganic acid derivative having a hydroxyterephthalic acid moiety by spectroscopic analysis together with chemical evidence, while 2 and 3 were elucidated to be a rutinosylxanthone and a glucosylxanthone, respectively. The absolute configurations of the sugar moieties of 2 and 3 were determined by HPLC analysis. The isolated compounds were evaluated for their inhibitory activities against erastin-induced ferroptosis on human hepatoma Hep3B cells and LPS-stimulated IL-1ß production from murine microglial cells.
Assuntos
Ferroptose , Gentianaceae , Xantonas , Camundongos , Humanos , Animais , Glucosídeos Iridoides , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Xantonas/farmacologiaRESUMO
Three new farnesylated coumarins, communiferulins A-C (1-3), and a farnesylated chromone, ferchromone (4), were isolated from the roots of an Apiaceous plant Ferula communis. Their structures including the relative configurations were elucidated by a combination of spectroscopic analyses and calculations of the NMR data. Communiferulins A-C (1-3) had dihydrofuran rings fused to C-3 and C-4 of their coumarin moieties, while 3 possessed one additional furan ring. HPLC analyses using a chiral column showed 1-4 to be racemates, and the absolute configurations of (+)-1, (-)-1, (+)-2, and (-)-2 were deduced by comparison of their ECD spectra with TDDFT-calculated spectra. Communiferulins A (1) and B (2), and ferchromone (4) showed inhibitory activities on IL-1ß production from LPS-stimulated microglial cells.
Assuntos
Ferula , Ferula/química , Estrutura Molecular , Extratos Vegetais/química , Espectroscopia de Ressonância Magnética , Cumarínicos/farmacologia , Cumarínicos/química , Raízes de Plantas/químicaRESUMO
Four new diterpene esters, shirakindicans A-D (1-4), along with eight related known diterpene esters (5-12), were isolated from the fruits of the Bangladeshi medicinal plant Shirakiopsis indica. The structures of 1-4 were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Shirakindican A (1) was assigned as a tigliane-type diterpene ester possessing an unusual 6ß-hydroxy-1,7-dien-3-one structure, while shirakindican B (2) exhibits a tiglia-1,5-dien-3,7-dione structure. The anti-HIV activities of the isolated diterpene esters were evaluated and showed significant activities for sapintoxins A (5) and D (11), with EC50 values of 0.0074 and 0.044 µM, respectively, and TI values of 1â¯100 and 5â¯290. Sapatoxin A (12) also exhibited anti-HIV activity with an EC50 value of 0.13 µM and a TI value of 161.
Assuntos
Fármacos Anti-HIV , Euphorbiaceae , HIV , Ésteres de Forbol , Euphorbiaceae/química , Frutas/química , Estrutura Molecular , HIV/efeitos dos fármacos , Ésteres de Forbol/química , Ésteres de Forbol/isolamento & purificação , Ésteres de Forbol/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Linhagem Celular , HumanosRESUMO
Propolis, a resinous substance produced by honeybees, has been used in folk medicine since ancient times due to its many biological benefits such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Propolis contains flavonoids, terpenoids, aromatic aldehydes, and alcohols, which vary with different climate and environmental conditions. In our study, we examined the antiallergic activity of Brazilian green propolis (BGP) and isolated the active compound that can suppress an allergy-sensitive gene, IL-33, expression and eosinophilia. Ethanolic extract of BGP freeze-dried powder was fractionated with several solvent systems, and the active fractions were collected based on activity measurement. The single active compound was found by thin-layer chromatography. Using column chromatography and NMR, the active compound was isolated and identified as 3,5,7-trihydroxy-6,4'-dimethoxyflavone, also known as betuletol. Further, the antiallergic activity of that has been examined in PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. Our data showed the IL-33 gene suppression both by BGP and the isolated active compound, betuletol. We also found that betuletol suppressed ERK phosphorylation, suggesting it could be effective in suppressing IL-33 mediated eosinophilic chronic inflammation and will provide new insights to develop potent therapeutics against allergic inflammations.
Assuntos
Antialérgicos , Eosinofilia , Própole , Animais , Expressão Gênica , Inflamação , Interleucina-33/genética , Camundongos , Própole/química , Própole/farmacologiaRESUMO
Intramolecular S-acylation of a thiol-installed threonine with a thioester unit, followed by S-O acyl transfer and subsequent desulphurisation, allows the synthesis of lactone peptides. A protocol has been developed enabling the cyclisation of a linear peptide, a reaction which has not been achieved by conventional methods.
Assuntos
Lactonas/química , Peptídeos/síntese química , Compostos de Sulfidrila/química , Treonina/química , Estrutura Molecular , Peptídeos/químicaRESUMO
Two new guaianolide sesquiterpenes, lanicepines A (1) and B (2), possessing unusual amino acid-derived substituents at C-13, were isolated from the flowering aerial parts of Saussurea laniceps, a traditional herbal medicine also known as "snow lotus". The structures of 1 and 2 were elucidated based on spectroscopic analysis including applications of the modified Mosher's method and Marfey's method as well as ECD calculations. Lanicepine A (1) contains a dihydropyridinone moiety with a carbamoyl and a hydroxymethyl group. This substituent was considered to consist of asparagine and a C4 unit. In contrast, lanicepine B (2) has a substituent that seems to be derived from l-proline and a C4 unit. Lanicepines A (1) and B (2) and two related known sesquiterpenes isolated from the same plant material, 11ß,13-dihydrodesacylcynaropicrin (3) and 11ß,13-dihydrodesacylcynaropicrin 8-O-ß-d-glucoside (4), demonstrated inhibitory activity against IL-1ß production from LPS-stimulated microglial cells.
Assuntos
Saussurea , Sesquiterpenos , Aminoácidos/análise , Estrutura Molecular , Componentes Aéreos da Planta/química , Saussurea/química , Sesquiterpenos/química , Sesquiterpenos de Guaiano/químicaRESUMO
Two new glycosides of methyl everninate, rhodomollosides A (1) and B (2), were isolated from the aerial parts of a medicinal plant Rhododendron molle. The structures of 1 and 2 were elucidated on the basis of detailed spectroscopic analyses as well as HPLC analyses for thiazolidine derivatives of their sugar moieties. The sugar moiety of rhodomolloside A (1) was elucidated to be a rare monosaccharide, D-allose, while rhodomolloside B (2) was assigned as a D-glucoside of methyl everninate. Furthermore, they were evaluated for their cytotoxicity against RAW264.7 cells, and for their inhibitory effects with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW 264.7 cells model.
Assuntos
Diterpenos , Rhododendron , Camundongos , Animais , Rhododendron/química , Glicosídeos/farmacologia , Diterpenos/química , Estrutura Molecular , Açúcares , Componentes Aéreos da PlantaRESUMO
Traditional herbal medicines, which have been used in the matured traditional medical systems as well as those have been used in ethnic medical systems, are invaluable resources of drug seeds. Ethnobotanical and ethnopharmacological survey may provide useful information of these herbal medicines, which are valuable for searching new bioactive molecules. From this viewpoint, we have been performing the ethnobotanical and ethnopharmacological field studies in Yunnan Province and Guangxi Zhuang Autonomous Region, China, and Mongolia. Phytochemical studies on traditional herbal medicines were performed based on the information obtained by our ethnobotanical survey. Herbal medicines used in Uzbekistan and Bangladesh were also investigated on the basis of the ethnopharmacological information obtained from collaborative researchers in the respective regions. Some studies were carried out for searching active substance(s) based on bioassay-guided fractionation and isolation. Over 150 new molecules were isolated in these studies, and their various biological activities were also demonstrated. This review summarizes the results of phytochemical studies of those traditional herbal medicines as well as biological activities of the isolated molecules.
Assuntos
Plantas Medicinais , China , Etnobotânica , Etnofarmacologia , Compostos Fitoquímicos , FitoterapiaRESUMO
Six dibenzo-1,4-dioxane derivatives (1-6) were isolated from the roots of a Hypericaceous plant Hypericum ascyron. Spectroscopic analyses revealed 2 and 4-6 to be new compounds. The partial racemic natures of 1-3 were concluded by chiral HPLC analyses, while 5 was confirmed to be a racemate. The absolute configurations 1-4 were deduced on the basis of ECD calculations. Biological activity evaluation of the dibenzo-1,4-dioxane derivatives along with two related compounds: hyperdioxanes A (7) and B (8), previously isolated from the same plant material by our group demonstrated that 7 exhibit an anti-HIV activity (IC50 5.3 µM, TI 7.2) while 8 showed an inhibitory effect on IL-1ß production (inhibition rate: 72.3% at 6.3 µM) from LPS-stimulated microglial cells.
Assuntos
Hypericum , Dioxanos , Estrutura Molecular , Raízes de PlantasRESUMO
Phytochemical study on a non-medicinal part of a plant material for herbal medicine, the roots of Schisandra chinensis, was conducted to isolate five new triterpenes, schinensins A-D (1-4) and 3-O-methylchangnanic acid (5), together with 21 known compounds including 10 triterpenes, one sterol, two sesquiterpenes, seven lignans, and one flavonoid. The structures of new triterpenes (1-5) were assigned on the basis of spectroscopic analyses aided with TDDFT ECD calculations. Schinensin A (1) was a dinortriterpene possessing 28-norschiartane skeleton, while schinensins B-D (2-4) were assigned as 3,4:9,10-disecocycloartane, 3,4-secocycloartane, and cycloartane triterpenes, respectively. In an evaluation of antiproliferative activities against human cancer cell lines, some triterpenes exhibited significant activities against human breast carcinoma MCF-7 cells as compared to the other cell lines (A549, HeLa, and RPMI8226).
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Schisandra/química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Humanos , Japão , Lignanas , Células MCF-7 , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Sesquiterpenos , Triterpenos/isolamento & purificaçãoRESUMO
Plants belonging to the genus Hypericum (Hypericaceae) are recognized as an abundant source of natural products with interesting chemical structures and intriguing biological activities. In the course of our continuing study on constituents of Hypericum plants, aiming at searching natural product-based lead compounds for therapeutic agents, we have isolated more than 100 new characteristic metabolites classified as prenylated acylphloroglucinols, meroterpenes, ketides, dibenzo-1,4-dioxane derivatives, and xanthones including prenylated xanthones, phenylxanthones, and xanthonolignoids from 11 Hypericum plants and one Triadenum plant collected in Japan, China, and Uzbekistan or cultivated in Japan. This review summarizes their chemical structures and biological activities.
Assuntos
Hypericum/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Produtos Biológicos , China , Japão , Estrutura Molecular , Prenilação , UzbequistãoRESUMO
Phytochemical investigation on the aerial parts of a Lamiaceous medicinal plant Perovskia scrophulariifolia collected in Uzbekistan resulted in the isolation of two new 20-norabietane diterpenes, along with thirteen known diterpenes including one 20-norabietane, eight abietanes, one 6,7-secoabietane, and three icetexanes. The structures of new 20-norabietane diterpenes, perovsfolins C (1) and D (2), were elucidated by spectroscopic analyses aided with calculations of ECD spectra. Perovsfolin C (1) is the first 20-norabietane diterpene possessing a 1,11-epoxy moiety, while perovsfolin D (2) is a 20-norabitetane diterpene with a 2-hydroxy-1,4-quinone moiety as C-ring. Anti-neuroinflammatory activity of the isolated diterpenes on microglial cells was evaluated.
Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Microglia/efeitos dos fármacos , Salvia/química , Abietanos/isolamento & purificação , Abietanos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Plantas Medicinais/química , UzbequistãoRESUMO
Structurally unique C28 terpenoids, perovsfolins A (1) and B (2), were isolated from the aerial parts of an Uzbek medicinal plant, Perovskia scrophulariifolia (Lamiaceae). Their chemical structures including an unprecedented 6/8/6/6/6 pentacyclic carbon skeleton with a C6-C3 ester moiety were elucidated on the basis of spectroscopic analyses aided by density functional theory calculations as well as chemical evidence. Perovsfolin B (2) exhibited an anti-neuroinflammatory activity.
Assuntos
Anti-Inflamatórios/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Salvia/química , Terpenos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Estrutura Molecular , Plantas Medicinais , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
Exploration for specialized metabolites of Okinawan marine sponges Agelas spp. resulted in the isolation of five new bromopyrrole alkaloids, agesasines A (1) and B (2), 9-hydroxydihydrodispacamide (3), 9-hydroxydihydrooroidin (4), and 9E-keramadine (5). Their structures were elucidated on the basis of spectroscopic analyses. Agesasines A (1) and B (2) were assigned as rare bromopyrrole alkaloids lacking an aminoimidazole moiety, while 3-5 were elucidated to be linear bromopyrrole alkaloids with either aminoimidazolone, aminoimidazole, or N-methylated aminoimidazole moieties.
Assuntos
Agelas/química , Alcaloides/isolamento & purificação , Células A549 , Alcaloides/química , Alcaloides/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Células MCF-7 , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologiaRESUMO
Five new abietane diterpenes, lophachinins A-E (1-5), and eleven known related diterpenes were isolated from a Mongolian traditional herbal medicine, the aerial parts of Lophanthus chinensis (Lamiaceae). The structures of new diterpenes were assigned by spectroscopic analyses. Lophachinins A (1) and B (2) were abietane diterpene possessing an endoperoxy bridge at C-ring. In contrast, lophachinins C-E (3-5) had an abietane skeleton with an aromatized C-ring. The absolute configuration of 1 was elucidated by application of the modified Mosher's method, while those of 2, 3, and 5 were assigned by chemical conversions. The absolute configuration of lophachinin D (4) was deduced by ECD calculation. Anti-inflammatory activity of isolated diterpenes on microglial cells were evaluated.
Assuntos
Abietanos/farmacologia , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Lamiaceae/química , Abietanos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Humanos , Medicina Tradicional do Leste Asiático , Microglia/efeitos dos fármacos , Estrutura Molecular , Mongólia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/químicaRESUMO
Four previously undescribed acylated iridoid glucosides, linaburiosides AâD, one undescribed iridoid, 7-deoxyiridolactonic acid, and one known acylated iridoid glucoside, iridolinarin C, were isolated from the aerial parts of a Mongolian traditional herbal medicine, Linaria buriatica. Linaburiosides AâD had an acyl moiety corresponding to 7-deoxyiridolactonic acid. Detailed spectroscopic analyses of linaburiosides AâD and 7-deoxyiridolactonic acid led to the assignment of their structures. The absolute configuration of 7-deoxyiridolactonic acid was elucidated by application of the PGME method; those of linaburiosides AâD were assigned on the basis of chemical conversions, as well as application of the modified Mosher's method. The absolute configuration of iridolinarin C was also elucidated in this study. Anti-inflammatory and antiproliferative activities of isolated compounds and their derivatives were evaluated.
Assuntos
Anti-Inflamatórios/farmacologia , Glucosídeos/farmacologia , Iridoides/farmacologia , Linaria/química , Compostos Fitoquímicos/farmacologia , Células A549 , Acilação , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Glucosídeos/química , Glucosídeos/isolamento & purificação , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/biossíntese , Iridoides/química , Iridoides/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Células MCF-7 , Microglia/efeitos dos fármacos , Microglia/metabolismo , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Células Tumorais CultivadasRESUMO
A new prenylated benzophenone, hypatulin C (1), was isolated from the leaves of Hypericum patulum together with a biogenetically related analog, hypelodin B (2). Hypatulin C (1) had a tricyclic [4.3.1.03,7]-decane moiety substituted by four prenyl groups. The structure of 1 was elucidated by detailed spectroscopic analyses, while the absolute stereochemistries of 1 and 2 were assigned by comparison of their ECD spectra with TDDFT calculated spectra.