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排序方式: 共有214条查询结果,搜索用时 15 毫秒
111.
Bringmann G Dreyer M Rischer H Wolf K Hadi HA Brun R Meimberg H Heubl G 《Journal of natural products》2004,67(12):2058-2062
Three new 5,1'-coupled naphthylisoquinoline alkaloids, ancistrobenomine A (1), 6-O-demethylancistrobenomine A (2), and 5'-O-demethylancistrocline (3), have been isolated from the stem bark of a botanically as yet undescribed highland liana Ancistrocladus sp., proposed to be named "A. benomensis" according to the region in Peninsular Malaysia where it has been discovered on the mountain of Gunung Benom. Two of the compounds possess an unprecedented structure with a novel hydroxymethylene group at C-3 of the fully dehydrogenated isoquinoline moiety. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. As typical of the so-called Ancistrocladaceae type, all of the compounds isolated bear an oxygen at C-6. Biological activities of these alkaloids against different protozoic pathogens are described. 相似文献
112.
Upregulation of P2X(7) receptor currents in Müller glial cells during proliferative vitreoretinopathy 总被引:1,自引:0,他引:1
Bringmann A Pannicke T Moll V Milenkovic I Faude F Enzmann V Wolf S Reichenbach A 《Investigative ophthalmology & visual science》2001,42(3):860-867
PURPOSE. Müller glial cells from the human retina express purinergic P2X(7) receptors. Because extracellular adenosine triphosphate (ATP) is assumed to be a mediator of the induction or maintenance of gliosis, this study was undertaken to determine whether the expression of these receptors is different in human Müller cells obtained from retinas of healthy donors and of patients with choroidal melanoma and proliferative vitreoretinopathy (PVR). METHODS. Human Müller cells were enzymatically isolated from donor retinas, and whole-cell patch-clamp recordings were made to characterize the density of the P2X(7) currents and the activation of currents through Ca2+-activated K+ channels of big conductance (I:(BK)) that reflects the increase of the intracellular Ca2+ concentration. RESULTS. Stimulation by external ATP or by benzoylbenzoyl ATP (BzATP) evoked both release of Ca2+ from thapsigargin-sensitive intracellular stores and opening of Ca2+ -permeable P2X(7) channels. These responses caused transient and sustained increases in I:(BK). In Müller cells from patients with PVR, the mean density of the BzATP-evoked cation currents was significantly greater compared with cells from healthy donors. As a consequence, such cells displayed an enlarged I:(BK) during application of purinergic agonists. ATP and BzATP increased the DNA synthesis rate of cultured cells. This effect could be reversed by blocking the I:(BK). CONCLUSIONS. The increased density of P2X(7) receptor channels may permit a higher level of entry of extracellular Ca2+ into cells from patients with PVR. Enhanced Ca2+ entry and the subsequent stronger activation of I:(BK) may contribute to the induction or maintenance of proliferative activity in gliotic Müller cells during PVR. 相似文献
113.
Bringmann G Günther C Saeb W Mies J Wickramasinghe A Mudogo V Brun R 《Journal of natural products》2000,63(10):1333-1337
Three new naphthylisoquinoline alkaloids, ancistrolikokines A-C (1-3), have been isolated and structurally assigned from Ancistrocladus likoko, as well as the known compound korupensamine A (4). Their 5,8'-coupling hints at a close biogenetic relationship of A. likoko to other Central African Ancistrocladus species. Compounds 1-4 showed good to moderate antimalarial activities when evaluated in vitro against the NF54 and K1 strains of Plasmodium falciparum. 相似文献
114.
Anthraquinones and betaenone derivatives from the sponge-associated fungus Microsphaeropsis species: novel inhibitors of protein kinases 总被引:3,自引:0,他引:3
Brauers G Edrada RA Ebel R Proksch P Wray V Berg A Gräfe U Schächtele C Totzke F Finkenzeller G Marme D Kraus J Münchbach M Michel M Bringmann G Schaumann K 《Journal of natural products》2000,63(6):739-745
An undescribed fungus of the genus Microsphaeropsis, isolated from the Mediterranean sponge Aplysina aerophoba, produces two new betaenone derivatives (1, 2) and three new 1,3,6, 8-tetrahydroxyanthraquinone congeners (5-7). The structures of the compounds were established on the basis of NMR spectroscopic and mass spectrometric data and by CD spectroscopy. This is the first report wherein the (1)H and (13)C NMR data of the betaenone congeners are fully and unambiguously assigned on the basis of two-dimensional NMR spectroscopy. Furthermore, we describe the first elucidation of the absolute configuration of 1-(2'-anthraquinonyl)ethanols such as 5 and 6, by quantum chemical calculation of their circular dichroism (CD) and comparison with experimentally measured spectra. Moreover, it was shown that compounds 1, 5, 6, and 7 are inhibitors of PKC-epsilon, CDK4, and EGF receptor tyrosine kinases. 相似文献
115.
Bringmann G Mühlbacher J Messer K Dreyer M Ebel R Nugroho BW Wray V Proksch P 《Journal of natural products》2003,66(1):80-85
Two rocaglamide-related natural products, the previously known compound 6-demethoxy-10-hydroxy-11-methoxy-6,7-methylendioxyrocaglamide (3), and cyclorocaglamide (4), its 8b,10-anhydro analogue, have been isolated from the tropical plant Aglaia oligophylla. Compound 4 is the first bridged cyclopentatetrahydrobenzofuran natural product, and it exhibited a CD spectrum virtually opposite that of all the other rocaglamide natural products known so far, but it still has the same absolute configuration at all stereogenic centers of the basic molecular framework. This was shown unequivocally by quantum chemical CD calculations (here based on molecular dynamics-weighted force field structures) and was finally confirmed experimentally, by a "biomimetic-type" cyclization of 3 to give 4, with the expected "inversion" of the CD spectrum. The opposite chiroptical properties of 3 and 4, despite their homochiral character, underline the necessity of handling chiroptical data with the greatest care, e.g., by simulating them by quantum chemical CD calculations. Compound 3 exhibited an LC(50) of 2.5 ppm when evaluated against neonate larvae of Spodoptera littoralis, while 4 was inactive in this assay up to 100 ppm. 相似文献
116.
PURPOSE: To detect the presence of voltage-gated Ca(2+) channels in the plasma membranes of freshly isolated Müller glial cells from the human retina and their modulation by GABA(B) receptor agonists. METHODS: Whole cell voltage-clamp recordings were made to study Ca( 2+), Ba(2+), and Na(+) currents through voltage-gated Ca(2+) channels. RESULTS: The vast majority of the investigated cells displayed no resolvable currents through Ca(2+) channels when Ca(2+) ions (2 mM) were present in the extracellular solution. Small-amplitude inwardly directed currents ( approximately 0.6 pA/pF) were detected when Ba(2+) ions (20 mM) were used as charge carrier. However, when Na(+) ions were used as charge carrier in divalent cation-free external solution, currents of large amplitudes ( approximately 7.5 pA/pF) through voltage-gated Ca(2+) channels were detected. Human Müller cells displayed currents through both transient, low voltage-activated Ca(2+) channels and long-lasting, high voltage-activated channels. The Na(+) fluxes through low voltage-activated Ca( 2+) channels were inhibited in a voltage-independent manner in the presence of GABA(B) receptor agonists. CONCLUSIONS: Human Müller glial cells express different kinds of voltage-gated Ca(2+) channels in their plasma membranes that can be activated only under certain physiological or pathophysiological conditions. The record of Na(+) fluxes in divalent cation-free solutions may be a technique to detect the presence of "hidden" voltage-gated Ca(2+) channels in Müller glial cells. 相似文献
117.
Activities of naphthylisoquinoline alkaloids and synthetic analogs against Leishmania major 下载免费PDF全文
Ponte-Sucre A Faber JH Gulder T Kajahn I Pedersen SE Schultheis M Bringmann G Moll H 《Antimicrobial agents and chemotherapy》2007,51(1):188-194
The current treatments for leishmaniasis are unsatisfactory due to their toxic side effects, high costs, and increasing problems with drug resistance. Thus, there is an urgent need for alternative drugs against leishmaniasis. Different approaches have been used to identify novel pharmacophores against Leishmania sp. parasites, and one strategy has been the analysis of naturally occurring plant-derived compounds, including naphthylisoquinoline alkaloids. In the present study, we examined the abilities of these alkaloids to inhibit the growth of Leishmania major promastigotes and evaluated their effects on macrophages, dendritic cells, and fibroblasts. Furthermore, we determined the efficacy of selected compounds in decreasing the infection rate of macrophages and regulating their production of cytokines and nitric oxide. Our results demonstrate that the naphthylisoquinoline alkaloids ancistrocladiniums A and B (compounds 10 and 11) and the synthetic isoquinolinium salt (compound 14) were effective against intracellular amastigotes in the low submicromolar range, while toxicity against mammalian cells was observed at concentrations that were significantly higher than those needed to impair parasite replication. The activities of compounds 11 and 14 were mainly directed against the amastigote stage of L. major. This effect was not associated with the stimulation of host macrophages to produce nitric oxide or secrete cytokines relevant for the leishmanicidal function. In conclusion, our data suggest that ancistrocladiniums A and B (compounds 10 and 11) and the synthetically prepared isoquinolinium salt (compound 14) are promising candidates to be considered as lead compounds for leishmanicidal drugs. 相似文献
118.
Enas Reda Abdelaleem Mamdouh Nabil Samy Taha F. S. Ali Muhamad Mustafa Mahmoud A. A. Ibrahim Gerhard Bringmann Safwat A. Ahmed Usama Ramadan Abdelmohsen Samar Yehia Desoukey 《RSC advances》2022,12(5):2992
In the current study, an investigation of the activity of the total extract of the marine sponge Spongia irregularis and its different fractions against the hepatitis C virus (HCV) was pursued. The results revealed that the ethyl acetate fraction exhibited the highest anti-HCV activity, with an IC50 value of 12.6 ± 0.05 μg ml−1. Chromatographic resolution of the ethyl acetate fraction resulted in the isolation of four known compounds, 1,3,7-trimethylguanine (1), 3,5-dihydroxyfuran-2(5H)-one (2), thymidine (3), and 1H-indazole (4). By using LC-HR-ESI-MS metabolic profiling, compounds 5–14 were also identified in the same fraction. Molecular docking calculations revealed the high binding affinity of compound 14 against the allosteric pocket of HCV NS3-NS4A and the active site of HCV NS3 helicase (−10.1 and −7.4 kcal mol−1, respectively). Molecular dynamics simulations, followed by molecular mechanics-generalized Born surface area energy calculations, demonstrated the structural and energetic stability of compound 14 in complex with HCV targets.Our study discusses the anti-HCV activity of Spongia irregularis. The results revealed that the ethyl acetate fraction exhibited the highest anti-HCV activity and Nakijiquinone F is the most likely anti-HCV candidate among the screened compounds. 相似文献
119.
Margrit Hollborn Solveig Tenckhoff Marlen Seifert Stephanie Köhler Peter Wiedemann Andreas Bringmann Leon Kohen 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2006,244(6):732-741
Background Placenta growth factor (PlGF) is an important co-factor in retinal neovascularization. To examine whether retinal pigment epithelial (RPE) cells may represent a source for PlGF during retinopathy, we determined whether human RPE cells in vitro produce and respond to PlGF. In addition, we determined whether the cells express receptors for PlGF, i.e. flt-1 and neuropilins.Methods Cultured human RPE cells of passages 3–5 were used. The regulation of the PlGF gene and protein expression by growth factors and cytokines was evaluated by quantitative PCR and ELISA. Proliferation rates and chemotaxis were determined by a bromodeoxyuridine and a Boyden chamber assay.Results Human RPE cells express mRNAs for various members of the vascular endothelial growth factor family and for their receptors, including mRNAs for PlGF, flt-1, KDR, and neuropilins-1 and -2. The expression levels of the mRNAs for neuropilins-1 and -2 were significantly higher than those for flt-1 and KDR. Members of the transforming growth factor (TGF)-β superfamily of growth factors (BMP-4, TGF-β1, and β2) were strong inducers of PlGF gene expression, and evoked secretion of PlGF-2 protein by RPE cells. Exogenous PlGF-2 induced chemotaxis in RPE cells and reduced slightly the cell proliferation at high concentrations.Conclusion The findings that RPE cells produce and respond to PlGF indicate that the factor exerts an autocrine/paracrine action on these cells. It is suggested that increased expression of TGF-β-related growth factors during diabetic retinopathy may cause PlGF secretion by RPE cells contributing to the stimulation of cell migration as a critical component of the progression of fibrovascular membranes. 相似文献
120.
Different modes of foveal regeneration after closure of full-thickness macular holes by (re)vitrectomy and autologous platelet concentrate 下载免费PDF全文
Andreas Bringmann Claudia Jochmann Jan Darius Unterlauft Renate Wiedemann Matus Rehak Peter Wiedemann 《国际眼科》2020,13(1):36-48
AIM: To describe using spectral-domain optical coherence tomography the regeneration of the foveal morphology after pars plana(re)vitrectomy surgery and gas tamponade combined with injection of autologous platelet concentrate to treat full-thickness macular holes, and to describe different anatomical outcome. METHODS: A retrospective case series of 8 eyes of 8 patients was described. RESULTS: In all cases investigated, the plateletassisted closure of macular holes was associated with a rapid resolution of cystic cavities in the foveal walls. In two patients, there was a regular regeneration of the foveal morphology after hole closure;the regenerated central fovea had a regular structure with a foveola and photoreceptors. In three other patients, there was an irregular regeneration of the fovea;a foveola was not formed, photoreceptor cells were absent from the foveal center, and the center was composed of Müller and retinal pigment epithelial(RPE) cells. The foveal regeneration after hole closure may proceed with or without a temporary detachment of the foveal center from the RPE, and with or without a direct contact between the central outer nuclear layer(ONL) and the RPE. Contacts between the ONL and RPE were observed only in patients with an irregular foveal regeneration after hole closure.CONCLUSION: The data show that there are different modes of foveal regeneration after closure of macular holes with(re)vitrectomy and platelet concentrate. It is suggested that the regular regeneration of the foveal morphology proceeds by Müller cell-mediated tissue movements without cell proliferation, whereas the irregular foveal regeneration proceeds in part by proliferation of Müller and RPE cells. 相似文献