RESUMO
Guided by 1H NMR spectroscopic experiments using the characteristic enol proton signals as probes, three pairs of new tautomeric cinnamoylphloroglucinol-monoterpene adducts (1-3) were isolated from the buds of Cleistocalyx operculatus. Their structures with absolute configurations were established by spectroscopic analysis, modified Mosher's method, and quantum chemical electronic circular dichroism calculation. Compounds 1-3 represent a novel class of cinnamoylphloroglucinol-monoterpene adducts featuring an unusual C-4-C-1' linkage between 2,2,4-trimethyl-cinnamyl-ß-triketone and modified linear monoterpenoid motifs. Notably, compounds 1-3 exhibited significant in vitro antiviral activity against respiratory syncytial virus (RSV).
Assuntos
Syzygium , Syzygium/química , Monoterpenos/química , Espectroscopia de Ressonância Magnética , Antivirais/química , Estrutura MolecularRESUMO
Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.
Assuntos
Lamiaceae , Sesquiterpenos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectrofotometria Infravermelho , Estrutura MolecularRESUMO
A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A-F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels-Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D-F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153).
Assuntos
Syzygium , Biomimética , Estereoisomerismo , Reação de Cicloadição , Antivirais/farmacologiaRESUMO
Inspired by a previously reported biomimetic synthesis study, four new naturally occurring phloroglucinol trimers 1-4 with unusual 6/5/5/6/6/6-fused hexacyclic ring systems, along with two known analogues (5 and 6) and two known biogenetically related dimers (10 and 11), were isolated from Rhodomyrtus tomentosa. Their structures and absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism calculation. By mimicking two potentially alternative biosynthetic pathways, the first asymmetric syntheses of 1-4 and the racemic syntheses of 5 and 6 were achieved in only five to six steps without the need for protecting groups. Furthermore, phloroglucinol dimers 10 and 11 exhibited significant in vitro antiviral activity against the respiratory syncytial virus.
Assuntos
Myrtaceae , Floroglucinol , Biomimética , Dicroísmo Circular , Estrutura Molecular , Myrtaceae/química , Floroglucinol/químicaRESUMO
Two-dimensional (2D) metal-organic framework (MOF) nanosheets, with largely exposed surface area and highly accessible active sites, have emerged as a novel kind of sensing material. Here, a luminescent 2D MOF nanosheet was designed and synthesized by a facile top-down strategy based on a three-dimensional (3D) layered MOF {[Zn(H2L)(H2O)2]·H2O}n (Zn-MOF; H4L = 3,5-bis(3',5'-dicarboxyphenyl)-1H-1,2,4-triazole). With a large π-conjugated system and rigid planar structure, ligand H4L was elaborately selected to construct the bulk Zn-MOF, which can be readily exfoliated into 2D nanosheets, owing to the weak interlayer interactions and easy-to-release H2O molecules in the interspaces of 2D layers. Given the great threat posed to the ecological environment by anti-inflammatory drugs and pesticides, the developed luminescent Zn-MOF nanosheets were utilized to determine these organic pollutants, achieving highly selective and sensitive detection of diclofenac sodium (DCF) and tetramethylthiuram disulfide (TMTD). Compared to the detection limits of 3D Zn-MOF (7.72 ppm for DCF, 6.01 ppm for TMTD), the obviously lower detection limits for 2D Zn-MOF nanosheets toward DCF (0.20 ppm) and TMTD (0.18 ppm) further revealed that the largely exposed surface area with rigid planar structure and ultralarge π-conjugated system greatly accelerated electron transfer, which brought about a vast improvement in response sensitivity. The remarkable quenching performance for DCF and TMTD stems from a combined effect of photoinduced electron transfer and competitive energy absorption. The possible sensing mechanism was systematically investigated by the studies of powder X-ray diffraction, UV-vis, luminescence lifetime, and density functional theory calculations.
Assuntos
Estruturas MetalorgânicasRESUMO
A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones GâP (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 µM.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Eurycoma/química , Leucemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Quassinas/farmacologia , Proliferação de Células , Células HL-60 , Humanos , Células K562 , Leucemia/patologiaRESUMO
Guided by 1H NMR spectroscopic experiments using the aromatic protons as probes, 11 macrocyclic diterpenes (1-11) were isolated from the aerial parts of Euphorbia helioscopia. Their full three-dimensional structures, including absolute configurations, were established unambiguously by spectroscopic analysis and single-crystal X-ray crystallographic experiments. Among the isolated compounds, compound 1 is the third member thus far of a rare class of Euphorbia diterpenes featuring an unusual 5/10 fused ring system, and 2-4 are new jatrophane diterpenes. Based on the NMR data of the jatrophane diterpenes obtained in this study as well as those with crystallographic structures reported in the literature, the correlations of the chemical shifts of the relevant carbons and the configurations of C-2, C-13, and C-14 of their flexible macrocyclic ring were considered. Moreover, the anti-inflammatory activities of 1-11 were investigated by monitoring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Compound 1 showed an IC50 of 7.4 ± 0.6 µM, which might be related to the regulation of the NF-κB signaling pathway by suppressing the translocation of the p65 subunit and the consequent reduction of IL-6 and TNF-α secretions.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Diterpenos/isolamento & purificação , Euphorbia/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cristalografia por Raios X , Diterpenos/química , Diterpenos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , NF-kappa B/fisiologia , Componentes Aéreos da Planta/química , Células RAW 264.7RESUMO
A new meroterpenoid, tomentodione E (1), along with four known ones (2-5) were isolated from the leaves of Rhodomyrtus tomentosa. Their structures were elucidated based on extensive spectroscopic data as well as computational methods. Compound 1 represents the first example of meroterpenoid possessing a sec-pentyl syncarpic acid motif coupled with a caryophyllene. Compounds 1-4 were evaluated for their in vitro antiviral activity against respiratory syncytial virus (RSV) with cytopathic effect (CPE) reduction assay, and 2 showed potent in vitro anti-RSV effect.
Assuntos
Antivirais/isolamento & purificação , Myrtaceae/química , Folhas de Planta/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Antivirais/química , Antivirais/farmacologia , Glicosídeos/química , Estrutura Molecular , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Terpenos/químicaRESUMO
Epithelial-mesenchymal transition plays an important role in many patho-physiological processes, including cancer invasion and metastatic progression. Hepatocyte nuclear factor 6 (HNF6) has been known to be an important factor for both physiological and pathological functions in liver and pancreas. However, its role in EMT and lung cancer progression remains unidentified. We observed that HNF6 level can be down-regulated by TGF-ß1 in human lung cancer cells. Knockdown of HNF6 induced EMT and increased cell migration. In contrast, ectopically expression of HNF6 inhibited cell migration and attenuated TGF-ß1-induced EMT. The data suggest that HNF6 plays a role in maintaining epithelial phenotype, which suppresses EMT. HNF6 also inhibits both colony formation and proliferation of lung cancer cells. It pronouncedly reduced the formation of tumor xenografts in nude mice. In addition, HNF6 can activate the promoter activity of p53 by directly binding to a specific region of its promoter and therefore increase the protein level of tumor suppressor p53. p53 knockdown induced EMT and increased cell migration, whereas the opposite effect was generated by p53 overexpression. p53 knockdown also inhibited the effect of HNF6 on EMT and cell migration, indicating that p53 is required for the functions of HNF6 herein. Moreover, there is a high positive correlation among the expression levels of HNF6, p53, and E-cadherin in human lung cancer cells and tissues. The data suggest that HNF6 inhibits EMT, cell migration, and invasive growth through a mechanism involving the transcriptional activation of p53.
Assuntos
Adenocarcinoma/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal , Fator 6 Nuclear de Hepatócito/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Animais , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Fator 6 Nuclear de Hepatócito/genética , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias , Ativação Transcricional/genética , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Proteína Supressora de Tumor p53RESUMO
Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.
RESUMO
Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.
Assuntos
Antivirais , Artocarpus , Flavonoides , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Artocarpus/química , Antivirais/química , Antivirais/farmacologia , Antivirais/isolamento & purificação , Estrutura Molecular , Herpesvirus Humano 1/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Folhas de Planta/química , Relação Estrutura-Atividade , Modelos MolecularesRESUMO
A phytochemical investigation on the buds of edible medicinal plant, Eugenia carvophyllata, led to the discovery of seven new compounds, caryophones A-G (1-7), along with two biogenetically-related known ones, 2-methoxy-7-methyl-1,4-naphthalenedione (8) and eugenol (9). Compounds 1-3 represent the first examples of C-5-C-1' connected naphthoquinone-monoterpene adducts with a new carbon skeleton. Compounds 4-7 are a class of novel neolignans with unusual linkage patterns, in which the C-9 position of one phenylpropene unit coupled with the aromatic core of another phenylpropene unit. The chemical structures of the new compounds were determined based on extensive spectroscopic analysis, X-ray diffraction crystallography, and quantum-chemical calculation. Among the isolates, compounds (-)-2, 3, 6, and 9 showed significant in vitro inhibitory activities against respiratory syncytial virus (RSV)-induced nitric oxide (NO) production in RAW264.7 cells.
Assuntos
Anti-Inflamatórios , Eugenia , Lignanas , Naftoquinonas , Óxido Nítrico , Compostos Fitoquímicos , Camundongos , Células RAW 264.7 , Animais , Óxido Nítrico/metabolismo , Estrutura Molecular , Lignanas/farmacologia , Lignanas/isolamento & purificação , Lignanas/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Naftoquinonas/farmacologia , Naftoquinonas/isolamento & purificação , Naftoquinonas/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Eugenia/química , Vírus Sinciciais Respiratórios/efeitos dos fármacos , ChinaRESUMO
This study was to investigate whether or not the dysfunction of atrial repolarization and abnormality of the intracellular Ca(2+) handling protein was augmented with ageing. Four groups of dogs were studied, adult and aged dogs in sinus rhythm (SR) and atrial fibrillation (AF) induced by rapid atrial pacing. We used whole cell patch clamp recording techniques to measure L-type Ca(2+) current in cardiomyocytes dispersed from the left atria. Expressions of the Ca(2+) handling protein were measured by real-time quantitative reverse transcription-polymerase chain reaction and Western blot methods. Cardiomyocytes from old atria showed longer action potential (AP) duration to 90% repolarization, lower AP plateau potential and peak L-type Ca(2+) current densities at both age groups in SR. AF led to a higher maximum diastolic potential, an increase of amplitude of phase 0, decreases of AP duration to 90% repolarization, plateau potential and peak L-type Ca(2+) current densities. Compared to the adult group, mRNA and protein expressions of the L-type calcium channel a1c were decreased, whereas expressions of calcium adenosine triphosphatase were increased in the aged group. Compared to SR group, expressions of Ca(2+) handling protein except for phospholamban were significantly decreased in both age groups with AF. We conclude that these ageing-induced electrophysiological and molecular changes showed that general pathophysiological adaptations might provide a substrate conducive to AF.
Assuntos
Envelhecimento/patologia , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Fenômenos Eletrofisiológicos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Potenciais de Ação , Envelhecimento/metabolismo , Animais , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/metabolismo , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Cães , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Homeostase , Miocárdio/metabolismo , Miocárdio/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , UltrassonografiaRESUMO
Seven new secoiridoid glycosides (1-7), together with a known analogue (8), were isolated from the fruits of Ligustrum lucidum. Their structures with absolute configurations were determined by HR-ESI-MS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectroscopic analysis, as well as biogenetic consideration. Compounds 1 and 2 are the first examples of secoiridoid glycoside dimers featuring a rare rearranged oleoside-type secoiridoid moiety, and compounds 3-7 represent a new class of oleoside-type secoiridoid glycosides with unusual stereochemistry at C-1 position. A plausible biosynthetic pathway for this group of unusual secoiridoid glycosides was also proposed herein. In addition, the isolates were evaluated for their in vitro anti-inflammatory activity, and all tested compounds exhibited modest inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.
Assuntos
Glicosídeos Iridoides , Ligustrum , Glicosídeos Iridoides/farmacologia , Glicosídeos Iridoides/química , Ligustrum/química , Estrutura Molecular , Frutas/química , Anti-Inflamatórios/farmacologia , Glicosídeos/farmacologia , Glicosídeos/análiseRESUMO
Lead (Pb) is one of the most widespread and highly toxic heavy metals in the environment. The design and synthesis of adsorbent materials for the selective and efficient removal of Pb2+ from aqueous solution has received much attention. Herein, the ligand 4,4'-azoxydibenzoic acid with the O- group was elaborately selected to construct a novel Pr-based MOF for Pb2+ removal. The as-prepared MOF adsorbents with high stability exhibited ultra-high selectivity for Pb2+, even in the presence of various highly concentrated competitive ions (with the ratios from 1 : 5 to 1 : 50). Also, a high uptake capacity (560.26 mg g-1) can be achieved for the MOF material, due to the availability of sufficient adsorption sites. The strong electrostatic attraction and coordination interaction between the numerous active O- sites on MOF adsorbents and Pb2+ can account for the good adsorption performance for Pb2+, which was systematically verified by zeta potential, FT-IR and XPS studies.
RESUMO
Janus kinase 3 (JAK3) is a potential target for the treatment of hematological malignancies. Herein, we report the discovery of a series of new orally bioavailable irreversible JAK3 kinase inhibitors. The representative compound 12n potently inhibited JAK3 kinase activity with an IC50 value of 1.2 nM and was more than 900-fold selective over JAK1, JAK2, and Tyk2. Cell-based assays revealed that 12n significantly suppressed phosphorylation of JAK3 and the downstream effectors STAT3/5 and also robustly restrained proliferation of BaF3 cells transfected with JAK3M511I activating mutation and human leukemia U937 cells harboring JAK3M511I with IC50 values of 22.9 and 20.2 nM, respectively. More importantly, 12n showed reasonable pharmacokinetic (PK) properties, and oral administration of 12n at a dose of 50 mg/kg twice daily led to tumor regression in a U937 cell inoculated xenograft mouse model. Thus, 12n represents a promising lead compound for further optimization to discover new therapeutic agents for hematological malignancies.
Assuntos
Neoplasias Hematológicas , Leucemia , Animais , Furanos/farmacologia , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Janus Quinase 1 , Janus Quinase 3 , Leucemia/tratamento farmacológico , Camundongos , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Células U937RESUMO
Based on the typical HPLC-UV-MS profiles and characteristic 1H NMR signals, twelve new phloroglucinol-derived lipids (1-12), featuring a long linear aliphatic side chain, together with three known ones (13-15) were isolated from the ethanol extract of the leaves of Syzygium cumini. Their structures were elucidated on the basis of extensive NMR spectroscopic analyses and mass spectrometric data. Compounds 1-5 characterize an enolizable ß,ß'-tricarbonyl motif with a cyclohexa-3,5-dien-1-one core that is hitherto undescribed in phloroglucinol-derived lipids. Compounds 4 and 10-12 are novel phloroglucinol-derived lipids containing an uncommon methylene interrupted trans double bond in their polyunsaturated aliphatic side chains. A polyketide biogenetic pathway for those phloroglucinol-derived lipids was also proposed. In addition, the isolates were evaluated for their neuroprotective activities against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced Neuro-2a cell injury. Notably, compounds 1, 5, and 10-12 significantly improved viability of Neuro-2a cells after OGD/R damage.
Assuntos
Lipídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Floroglucinol/química , Syzygium/química , Animais , Linhagem Celular , China , Lipídeos/isolamento & purificação , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/químicaRESUMO
Transforming growth factor-beta (TGF-beta) can induce G2/M phase-dependent apoptosis and G1/S phase-dependent epithelial-mesenchymal transition (EMT) in hepatocytes, but the underlying mechanism remains poorly understood. In this study, we investigated alterations in the global proteome using two dimensional gel electrophoresis of AML-12 murine hepatocyte cells after treatment with TGF-beta at several time points after synchronization in the G2/M or G1/S phase. Upon TGF-beta treatment, the expression levels of 44 proteins were found to be significantly changed in cells synchronized in the G2/M phase. These proteins were identified by MALDI-TOF/TOF and classified into seven categories according to function. In addition, TGF-beta induced downregulation of glutamine synthetase in cells in G2/M but not G1/S phase, and this was further confirmed by immunoblotting. Moreover, exogenous glutamine completely blocked TGF-beta-induced apoptosis in G2/M and non-synchronized cells, whereas it had no effect on EMT, suggesting that the downregulation of glutamine synthetase is involved in G2/M phase-dependent apoptosis. These results provide new insight into the mechanism of the multifunctional effects of TGF-beta and how apoptosis and EMT are regulated in the same type of cells.
Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Animais , Apoptose/fisiologia , Ciclo Celular/fisiologia , Linhagem Celular , DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Eletroforese em Gel Bidimensional , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Glutamato-Amônia Ligase/metabolismo , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Potencial da Membrana Mitocondrial , Mesoderma/citologia , Mesoderma/efeitos dos fármacos , Mesoderma/metabolismo , Camundongos , Proteoma/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Multiple organ dysfunction syndrome (MODS)-specific cellular electrophysiological changes have so far not been reported and it seemed unlikely that they were related to arrhythmogenesis. METHODS AND RESULTS: Twelve dogs, weight 12 +/- 2 kg, were divided into a control group (n = 6) and an MODS group (n = 6). MODS lasting for 72 h was induced by the 'two-hit' method in 6 dogs. Ventricular myocytes were enzymatically isolated. Early afterdepolarizations (EADs), action potential duration (APD) and L-type calcium currents (ICa,L) were assessed. Sinus arrhythmias in all MODS dogs (100%; 6 of 6) and premature ventricular beats in 4 MODS dogs (66%; 4 of 6) were recorded, while no arrhythmias were found in the control animals. The prolongation of the APD was associated with a decreased ICa,L, and frequently provoked EADs were the typical electrophysiological alterations in the myocytes of MODS dogs. The action potential prolongation was shortened, the ICa,L blocked and EAD suppressed by using verapamil (100 micromol/l) in the myocytes of MODS dogs (66%; 4 of 6). CONCLUSION: The changes in cellular electrophysiology within 72 h in the heart of MODS dogs are APD prolongation, markedly decreased ICa,L as well as frequently provoked EAD, the most common types of arrhythmia being sinus arrhythmia and premature ventricular beats. This study suggests that verapamil appears to be an effective agent in reversing alterations in cellular electrophysiology at the early stage of MODS.
Assuntos
Arritmias Cardíacas/etiologia , Insuficiência de Múltiplos Órgãos/complicações , Potenciais de Ação , Animais , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Pressão Sanguínea , Canais de Cálcio Tipo L/metabolismo , Células Cultivadas , Cães , Técnicas Eletrofisiológicas Cardíacas , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/fisiopatologia , Miócitos Cardíacos/fisiologia , Verapamil/uso terapêuticoRESUMO
The phytochemical study of the aerial part of Mesona chinensis led to the isolation of five new caffeic acid oligomers (1-5), as well as four known analogues (6-9). The structures of the new compounds including their absolute configurations were elucidated by comprehensive spectroscopic analysis, chemical method, and quantum-chemical electronic circular dichroism (ECD) calculation. Among the isolates, compound 7 showed significant in vitro antiviral activity on respiratory syncytial virus (RSV).