RESUMO
Amyotrophic lateral sclerosis (ALS) is a devastating motor disease with limited treatment options. A domestic fungal extract library was screened using three assays related to the pathophysiology of ALS with the aim of developing a novel ALS drug. 2(3H)-dihydrofuranolactones 1 and 2, and five known compounds 3-7 were isolated from Pleosporales sp. NUH322 culture media, and their protective activity against the excitotoxicity of ß-N-oxalyl-L-α,ß-diaminopropionic acid (ODAP), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamatergic agonist, was evaluated under low mitochondrial glutathione levels induced by ethacrynic acid (EA) and low sulfur amino acids using our developed ODAP-EA assay. Additional assays evaluated the recovery from cytotoxicity caused by transfected SOD1-G93A, an ALS-causal gene, and the inhibitory effect against reactive oxygen species (ROS) elevation. The structures of 1 and 2 were elucidated using various spectroscopic methods. We synthesized 1 from D-ribose, and confirmed the absolute structure. Isolated and synthesized 1 displayed higher ODAP-EA activities than the extract and represented its activity. Furthermore, 1 exhibited protective activity against SOD1-G93A-induced toxicity. An ALS mouse model, SOD1-G93A, of both sexes, was treated orally with 1 at pre- and post-symptomatic stages. The latter treatment significantly extended their lifespan (p = 0.03) and delayed motor deterioration (p = 0.001-0.01). Our result suggests that 1 is a promising lead compound for the development of ALS drugs with a new spectrum of action targeting both SOD1-G93A proteopathy and excitotoxicity through its action on the AMPA-type glutamatergic receptor.
Assuntos
Esclerose Lateral Amiotrófica , Camundongos , Masculino , Feminino , Animais , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Neurônios Motores/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Camundongos Transgênicos , Superóxido Dismutase/metabolismo , Medula Espinal/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismo , Modelos Animais de DoençasRESUMO
Genus Dendrobium (Orchidaceae) contains numerous species. Phylogenetic analyses based on morphological characteristics and DNA sequences indicated that this genus is divided into two major groups: Asian and Australasian clades. On the other hand, little is known about the phytochemical differences and similarities among the species in each clade. In this study, we selected 18 Dendrobium species (11 from the Asian clade and 7 from the Australasian clade) and constructed HPLC profiles, arrays composed of relative intensity of the chromatographic peaks. Next, orthogonal partial least square discriminant analysis (OPLS-DA) was applied to the profile matrix to classify Dendrobium species into the Asian and Australasian clades in order to identify the peaks that significantly contribute to the class separation. In the end, two phenanthrenes, 4,9-dimethoxyphenanthrene-2,5-diol 1 and 1,5-dimethoxyphenanthrene-2,7-diol 2, which contributed to the class separation, were isolated from the HPLC peaks. The existence of 2 was limited to the genetically related Australasian species.
Assuntos
Dendrobium/química , Fenantrenos/análise , Extratos Vegetais/análise , Australásia , Cromatografia Líquida de Alta Pressão , Análise Multivariada , Especificidade da EspécieRESUMO
From the bark of Ladenbergia hexandra Klotzsch, ten triterpenoid glycosides were isolated along with five known compounds, and their structures were determined based on extensive NMR and mass spectroscopic, GC and HPLC analyses. Some triterpenoid glycosides contained 6-deoxy-D-allose or D-allose as a sugar moiety. The absolute stereochemical assignment of the sugars was determined by comparison with synthetic samples, as well as by GC and HPLC analysis.
Assuntos
Glicosídeos/isolamento & purificação , Rubiaceae/química , Triterpenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Cimenos , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Estrutura Molecular , Monoterpenos , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Triterpenos/químicaRESUMO
Two new humulene-type sesquiterpenes, named hyptishumulene I (1) and II (2), have been isolated, together with eight known compounds, a humulene-type sesquiterpene (3), a monoterpene (4) and six abietane-type diterpenoids (5-10) from the aerial parts of Hyptis incana (Labiatae). The cytotoxic activity of the isolated compounds against mouse leukemia cells (L1210) was examined. The abietane-type diterpenoids (5-10) showed rather potent growth inhibitory activity (IC50<15 microM), while the new humulene-type compounds (1 and 2) exhibited moderate activity (IC50>50 microM).
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Hyptis/química , Sesquiterpenos/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia L1210/tratamento farmacológico , Camundongos , Estrutura Molecular , Sesquiterpenos Monocíclicos , Fitoterapia , Extratos Vegetais/uso terapêutico , Sesquiterpenos/uso terapêuticoRESUMO
BACKGROUND: Neuroblastoma is one of the most commonly encountered solid tumors in the pediatric age group, and the prognosis of patients with advanced neuroblastoma is very poor. In this study, the antitumor effects of five phenolic diterpenes derived from Hyptis incana (Lamiaceae), a Brazilian medicinal plant, were examined on neuroblastoma cells. MATERIALS AND METHODS: Cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic nuclear shrinkage was monitored by Hoechst 33342 staining. The cell-cycle status was evaluated by flow cytometry and protein alterations were monitored by western blotting. Differentiated cells were photographed and counted in a randomized fashion. RESULTS: All of the examined compounds exhibited significant cytotoxicity towards the neuroblastoma cells. In particular, 7-ethoxyrosmanol had a high degree of efficacy. Nuclear condensation and degradation of procaspase-3 and -9 were observed after treatment of the cells with these compounds. Moreover, phenolic diterpenes induced cell-cycle arrest in the G(2)/M phase. Rosmanol and epirosmanol tended to induce differentiation. CONCLUSION: Phenolic diterpenes isolated from H. incana have multiple antitumor effects on neuroblastoma cells.
Assuntos
Apoptose/efeitos dos fármacos , Diterpenos/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Neuroblastoma , Extratos Vegetais/farmacologia , Abietanos , Western Blotting , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Hyptis/química , Fenóis/farmacologiaRESUMO
Three new monoterpene glucosides, ziziphoroside A (1), B (2), and C (3), together with fifteen known compounds were isolated from the whole herb of Z. clinopodioides. The structures of new compounds were determined primarily from 1D-, 2D-NMR and circular dichroism (CD) spectroscopic analyses. The isolated compounds were evaluated for their inhibitory activity against nitric oxide (NO) production by lipopolysaccharide (LPS) and interferon (IFN)-γ activated macrophages, RAW 264.7. Shizonepetoside A (8) and flavones (11, 12, 13) showed potent inhibitory activity against NO production.
Assuntos
Glucosídeos/química , Lamiaceae/química , Monoterpenos/química , Animais , Linhagem Celular , Dicroísmo Circular/métodos , Flavonas/química , Flavonas/isolamento & purificação , Flavonas/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Camundongos , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas Medicinais/químicaRESUMO
Two flavanones, 5,2',6'-trihydroxy-7,8-dimethoxyflavanone (1), 5,2',6'-trihydroxy-6,7,8-trimethoxyflavanone (2) and their 2'-O-ß-D-glucosides (3, 4), and a neoclerodane-type diterpene, 15-demethoxyscupolin I (5), together with twenty-eight known compounds were isolated from the extracts of Lagochilus leiacanthus. The structures of the new compounds were determined by spectroscopic means. The two new flavanones and some known flavonoids showed the inhibitory activity on the release of ß-hexosaminidase from RBL-2H3 cells.
Assuntos
Flavanonas/química , Flavanonas/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Lamiaceae/química , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , Animais , Linhagem Celular , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Flavanonas/isolamento & purificação , Flavonoides/isolamento & purificação , Ratos , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
Monoterpenoids (3 and 4), sesquiterpenoid (2), diterpenoid (1) and four phenethyl glucosides (5-8), together with fourteen known compounds, were isolated from the whole herb of Hyssopus cuspidatus. Their structures were determined by spectroscopic means. The abietane-type diterpenoids (1, 9, 10), rosmarinic acid (15) and salvigenin (17) inhibited leukotriene (LT) C(4) secretion from primary alveolar cells of Wistar rats.
Assuntos
Glucosídeos/farmacologia , Lamiaceae/química , Leucotrieno C4/metabolismo , Extratos Vegetais/química , Terpenos/química , Animais , Feminino , Glucosídeos/química , Glucosídeos/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
A system consisting of meso-5,10,15,20-tetramesitylporphyrinate osmium(II) carbonyl complex [Os(TMP)CO] as a precatalyst and tert-butylhydroperoxide (TBHP) as an oxygen donor is shown to be an efficient, regioselective oxidant system for the allylic oxidation, ketonization and hydroxylation of unactivated C-H bonds in a series of the peracetate derivatives of penta- and tetracyclic triterpenoids. Treatment of the substrates with this oxidant system afforded a variety of novel or scarce oxygenated derivatives in one-step. Structures of the isolated components, after chromatographic separation, were determined by spectroscopic methods including GC-MS and shift-correlated 2D-NMR techniques. Factors governing the regioselectivity and the possible mechanism for the oxyfunctionalization of the unactivated carbons are also discussed.
Assuntos
Complexos de Coordenação/química , Osmio/química , Triterpenos/química , terc-Butil Hidroperóxido/química , Catálise , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Oxirredução , EstereoisomerismoRESUMO
Two sets of new diastereomeric 4-nonylphenol (NP) isomers [4-(3,4-dimethylheptan-4-yl)phenol (344NP, NP-J, L) and 4-(3,4-dimethylheptan-3-yl)phenol (343NP, NP-K, P)] were separated from a commercial NP mixture. The mixture of these diastereomers was synthesized at the same time by a single Friedel-Crafts reaction of 3,4-dimethyl-4-heptanol and phenol, and the mixture was separated into individual NPs by HPLC equipped with Hypercarb column. For the first time, in this study the stereostructure-estrogenic activity relationship of NP diastereomers was investigated. The NP isomers (NP-L and NP-P) having the beta-methyl group over the benzene ring were found to be 2-4 times more estrogenic than their diastereomers (NP-J and NP-K). In the case of the other set of diastereomer [4-(3,5-dimethylheptan-3-yl)phenol, (353NP, NP-E, G)] containing gamma-methyl group in the molecule, the gamma-methyl proton signal (delta 0.49) in the more estrogenic isomer (NP-G) also appeared in a higher field than the corresponding methyl signal (delta 0.76) of the less estrogenic isomer (NP-E).
Assuntos
Misturas Complexas/química , Estrogênios/síntese química , Estrogênios/isolamento & purificação , Fenóis/síntese química , Fenóis/isolamento & purificação , Estrogênios/química , Estrogênios/farmacologia , Humanos , Fenóis/química , Fenóis/farmacologia , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
We evaluated the effects of various lupane triterpenes on B16 2F2 mouse melanoma cell differentiation and proliferation. All of the compounds tested (numbered 1-6) induced melanogenesis of B16 2F2 cells, a marker of melanoma cell differentiation. Compounds 4-6, which have a carbonyl group at C-20, markedly inhibited the growth of B16 2F2 cells by the induction of apoptosis. Cytotoxic profiles of these lupane triterpenes against human cancer cells demonstrated that compounds 4-6 showed inhibitory effects on the proliferations of leukemia and lung cancer cells, to a greater extent than other cancer and normal fibroblast cells. These results suggest that the carbonyl group at C-20 of lupane triterpenes played important roles in their apoptosis-inducing activity against cancer cells.
Assuntos
Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Melaninas/biossíntese , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Extratos Vegetais/síntese química , Extratos Vegetais/química , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/químicaRESUMO
Eight branched 4-nonylphenol (NP) isomers, which were identified from commercially available NP reagent, 4-(1-ethyl-1,4-dimethylpentyl)phenol (NP-C), 4-(1,1-dimethyl-3-ethylpentyl)phenol (NP-D), 4-(1,3-dimethyl-1-ethylpentyl)phenol (NP-E(G)), diastereomeric mixture), 4-(1,1,4-trimethylhexyl)phenol (NP-F), 4-(1-methyl-1-n-propylpentyl)phenol (NP-H), 4-(1,1-dimethyl-2-ethylpentyl)phenol (NP-I), 4-(1,1,2-trimethylhexyl)phenol (NP-M), and 4-(1-ethyl-1-methylhexyl)phenol (NP-N), were synthesized by two different synthetic methods starting from 4-benzyloxyacetophenone or phenol. The chemical structures of the synthesized compounds were confirmed by MS and NMR spectroscopy. The estrogenic activities of these synthetic NP isomers were tested and exhibited different activities on the recombinant yeast screen system. NP-I was found to exhibit three times greater estrogenic activity than the commercial NP mixture.
Assuntos
Disruptores Endócrinos/síntese química , Disruptores Endócrinos/toxicidade , Estrogênios , Fenóis/síntese química , Fenóis/toxicidade , Bioensaio , Disruptores Endócrinos/química , Humanos , Isomerismo , Fenóis/química , Leveduras/efeitos dos fármacos , Leveduras/metabolismoRESUMO
Thirteen isomers of branched para-nonylphenols (para-NP) in three technical mixtures were isomer-specifically determined using their synthesized standards by SIM of structurally specific ions, m/z 135, 149 or 163 with GC-MS. Of the 13 isomers, four isomers, 4-(2,4-dimethylheptan-4-yl)phenol, 4-(4-methyloctan-4-yl)phenol, 4-(3-ethyl-2-methylhexan-2-yl)phenol (3E22NP) and 4-(2,3-dimethylheptan-2-yl)phenol synthesized for their determinations were first used as standard substances. The 13 isomers in the technical mixtures individually occurred at mass percent portion of more than 2%. The total mass percent portions in the mixtures from Tokyo Chemical Industry (TCI), Aldrich, and Fluka covered with 89+/-2%, 75+/-4% and 77+/-2%, respectively. The abundance of 4-(3,6-dimethylheptan-3-yl)phenol in the three mixtures was the largest with 11.1+/-2% to 9.9+/-0.3%, while that of 4-(2-methyloctan-2-yl)phenol was the smallest with 2.9+/-0.3% to 3.0+/-0.2%. Additionally, structures of four new isomers of more than 1% portion present in a technical mixture were elucidated as two pairs of diastereomeric isomers: two types of 4-(3,4-dimethylheptan-4-yl)phenol (344NP) and those of 4-(3,4-dimethylheptan-3-yl)phenol (343NP). By estrogenic assay of 13 isomers with yeast estrogen screen system, the activity of 3E22NP was the highest, while that of 4-(3-methyloctan-3-yl)phenol was the least. Their relative activities to that of 3E22NP were individually calculated. Estrogenic equivalent concentrations of the three technical mixtures were predictively evaluated. The ratio of the EEC to the conventional concentration, total mass percent portions of the 13 isomers in technical mixtures were 0.208 for TCI, 0.206 for Aldrich and 0.205 for Fluka. The predicted estrogenic activity of measured concentration of para-NP in technical mixtures was approximately 5-fold greater than the measured estrogen agonist activity.
Assuntos
Estrogênios/análise , Estrogênios/metabolismo , Fenóis/análise , Fenóis/metabolismo , Receptores de Estrogênio/metabolismo , Estrogênios/química , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Isomerismo , Fenóis/química , Receptores de Estrogênio/genética , Padrões de Referência , Leveduras/genética , beta-Galactosidase/metabolismoRESUMO
The pharmacological profiles of the novel acid pump antagonist 7-(4-fluorobenzyloxy)-2,3-dimethyl-1-{[(1S,2S)-2-methylcyclopropyl]methyl}-1H-pyrrolo[2,3-d]pyridazine (CS-526) were investigated in terms of hog gastric H+,K+-ATPase activity, gastric acid secretion, and acute gastroesophageal lesions in comparison with other proton pump inhibitors (PPIs). CS-526 inhibited H+,K+-ATPase activity in a concentration-dependent manner, with an IC50 value of 61 nM. The inhibitory effect of CS-526 on H+,K+-ATPase activity was more potent than that of any of the other PPIs examined. The inhibitory mechanism of CS-526 on H+,K+-ATPase was a competitive antagonism to the K+ binding site of H+,K+-ATPase, and it was also a reversible inhibition. In pylorus-ligated rats, intraduodenal or oral administration of CS-526 inhibited gastric acid secretion in a dose-dependent manner, and the ID50 values were 2.8 or 0.7 mg/kg, respectively. In Heidenhain pouch dogs, intrapouch administration of CS-526 inhibited histamine-stimulated gastric acid secretion in a dose- and retention time-dependent manner. In a reflux esophagitis model, intraduodenal and oral administration of CS-526 prevented esophageal lesions with ID50 values of 5.4 and 1.9 mg/kg, respectively. Lansoprazole prevented esophagitis only by intraduodenal administration (ID50 = 2.2 mg/kg). Furthermore, CS-526 inhibited acute gastric mucosal lesions. These data demonstrate that the novel acid pump antagonist CS-526 has potent antisecretory and antiulcer effects. These findings indicate that CS-526 would have a curative effect on gastroesophageal reflux disease via its potent antisecretory and antiulcer actions.
Assuntos
Inibidores Enzimáticos/farmacologia , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Inibidores da Bomba de Prótons , Piridazinas/farmacologia , Pirróis/farmacologia , Animais , Modelos Animais de Doenças , Cães , Inibidores Enzimáticos/química , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/metabolismo , Esofagite Péptica/patologia , Mucosa Gástrica/enzimologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/química , Rim/efeitos dos fármacos , Rim/enzimologia , Masculino , Estrutura Molecular , Piridazinas/química , Pirróis/química , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , SuínosRESUMO
Oxyfunctionalization of the bioactive terpenoids, ursolic acid acetate (1), oleanolic acid acetate (5), lupeol acetate (12), and kaurenic acid (17), with dimethyldioxirane (DMDO) was investigated. Treatment of the terpenoids with DMDO under mild conditions afforded a variety of oxidation and oxydegradation products to yield naturally occurring and/or novel compounds in one step. After chromatographic separation, the structures of the individual isolated products were determined using spectroscopic methods including several homonuclear (1H-1H) and heteronuclear (1H-13C) shift-correlated 2D-NMR techniques. The inhibitory activity of the terpenoid derivatives against alpha-glucosidase was investigated and compounds 1, 3, 7, and 9 were found to exhibit potent activity.
Assuntos
Compostos de Epóxi/farmacologia , Plantas Medicinais , Terpenos/farmacologia , alfa-Glucosidases/metabolismo , Acetatos/química , Acetatos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Compostos de Epóxi/química , Espectroscopia de Ressonância Magnética , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Oxirredução , Triterpenos Pentacíclicos , Terpenos/química , Triterpenos/química , Triterpenos/farmacologia , Ácido UrsólicoRESUMO
tert-Butyl hydroperoxide catalyzed by (5,10,15,20-tetramesitylporphyrinate) osmium(II) carbonyl [Os(TMP)CO] complex was found to be a highly efficient versatile oxidant for C-H carbons in steroid substrates. When reacted with representative steroids with an estrane, pregnane, 5beta-cholane, or 5alpha-cholestane structure, regioselective oxyfunctionalization and/or oxidative degradation occurred to give a variety of novel and uncommon derivatives in one step.
Assuntos
Carbono , Sistema Enzimático do Citocromo P-450/metabolismo , Compostos Organometálicos/metabolismo , Osmio , Porfirinas , Esteroides/metabolismo , terc-Butil Hidroperóxido/metabolismo , Colanos/química , Colanos/metabolismo , Sistema Enzimático do Citocromo P-450/química , Estranos/química , Estranos/metabolismo , Hidroxilação , Modelos Biológicos , Modelos Químicos , Compostos Organometálicos/química , Oxirredução , Pregnanos/química , Pregnanos/metabolismo , Esteroides/química , terc-Butil Hidroperóxido/químicaRESUMO
A new sesquiterpene, named baccharisketone (1), and a new monoterpene, p-methoxythymol acetate (2), were isolated from the leaves of Baccharis dracunculifolia along with seventeen known compounds (3-19). The structures of the new compounds were determined by spectroscopic means. The growth inhibitory activity of the isolated compounds against leukemia cells (L 1210) was tested and three terpene phenols (4, 6, 17) and five sesquiterpene alcohols (8, 10, 11, 13, 16) were found to exhibit strong cytotoxic activity.
Assuntos
Baccharis/química , Monoterpenos/química , Monoterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Monoterpenos/isolamento & purificação , Folhas de Planta/química , Sesquiterpenos/isolamento & purificação , EstereoisomerismoRESUMO
A new norditerpenoid alkaloid, manshuritine (1) has been isolated from Aconitum manshuricum, together with seven known alkaloids; beiwudine (2), beiwutine (3), 16-epi-pyromesaconitine (4), mesaconitine (5), aconitine (6), hypaconitine (7) and 14-benzoylmesaconine (8). The structure of the new compound was elucidated on the basis of spectral data and chemical correlations.
RESUMO
Concentrations of 4-nonylphenol (NP) were determined by isomer-specific quantification of individual NP isomers based on relative response factor (RRF) quantification with GC-MS in combination with steam distillation extraction. Concentrations of NP in the Ariake Sea decreased with distance from the river mouth (St.A; 49 ng NP/l) to offshore areas (St.C; 11 ng NP/l). Even the least concentration in water from St.C in Ariake Sea was sufficient to have adverse effects on barnacles. The isomers, NP1-NP14 were separated by GC-PFC and identified structurally with NMR. The isomers varied in estrogenic activity with NP7 exhibiting the greatest estrogenic activity with a potency that was approximately 1.9 x 10(-3) that of 17beta-estradiol (E2) in recombinant yeast screen system. The coefficient of variation (CV) of NP isomer's concentrations among three samples at St.A, B and C were 4-75%. This suggests that NP isomers might be independently degraded in aquatic environmental samples. The predicted estrogenic activity of measured concentrations of NP in Ariake Sea was 2.7-3.0-fold greater than the measured estrogen agonist activity.
Assuntos
Monitoramento Ambiental/estatística & dados numéricos , Estrogênios/análise , Fenóis/análise , Água do Mar/química , Poluentes Químicos da Água/análise , Cromatografia Gasosa-Espectrometria de Massas , Isomerismo , Japão , Espectroscopia de Ressonância Magnética , Oceanos e MaresRESUMO
Four ent-kaurenoic acid derivatives, 2beta,16alpha,17-trihydroxy-ent-kauran-19-oic acid (1), 3beta,16alpha,17-trihydroxy-ent-kauran-19-oic acid (2), 11alpha,15beta-dihydroxy-7-O-beta-d-glucopyranosyl-ent-kaur-16-en-19-oic acid (3) and 1alpha,15beta-dihydroxy-7-O-beta-d-glucopyranosyl-ent-kaur-16-en-19-oic acid (4), were isolated together with five known compounds, 1,5-dicaffeoyl-quinic acid (5), 2-O-glucosyloxy-4-methoxy-cinnamic acid (6), phenethyl alcohol glucoside (7), phenethyl-1-O-beta-d-apiofuranosyl (1-->2) beta-d-glucopyranoside (sayaendoside) (8) and 3,6-dihydroxy-beta-ion-9-ol (9) from the 50% aqueous acetone extract of the aerial parts of Mikania hirsutissima DC. (Compositae). Compounds 1-9 were tested for their proliferative activity toward peripheral blood mononuclear cells (hPBMC); compounds 1 and 2 showed significant activity (43.8% and 36.7%, at 100 microM, respectively) on the lymphocyte.