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Sohretoglu D.,Hacettepe University | Kuruuzum-Uz A.,Hacettepe University | Simon A.,Budapest University of Technology and Economics | Patocs T.,Budapest University of Technology and Economics | Dekany M.,Spectroscopic Research
Records of Natural Products | Year: 2014

Three new secondary metabolites kermesoside (1), cocciferoside (2) and (-)-8-chlorocatechin (3), were isolated from the the stems with barks of Quercus coccifera along with five known phenolic compounds, 3- hydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (4) and 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)- propan-1-one (5), trans-resveratrol-3-O-β-glucopyranoside (6) lyoniresinol-9-O-β-xylopyranoside (7), lyoniresinol-9-O-β-glucopyranoside (8). The structure elucidation of the isolated compounds was performed by spectroscopic methods (UV, 1D- and 2D- NMR and HR-MS). © 2014 ACG Publications. All rights reserved. Source


Lajter I.,University of Szeged | Vasas A.,University of Szeged | Beni Z.,Spectroscopic Research | Forgo P.,University of Szeged | And 7 more authors.
Journal of Natural Products | Year: 2014

Five new sesquiterpenes, neurolobatin A (1), neurolobatin B (2), 5β-hydroxy-8β-isovaleroyloxy-9α-hydroxycalyculatolide (3), 3-epi-desacetylisovaleroylheliangine (4), and 3β-acetoxy-8β- isovaleroyloxyreynosin (5), were isolated from the aerial parts of Neurolaena lobata. The structures were established by means of a combined spectroscopic data analysis, including ESIMS, APCI-MS, and 1D- and 2D-NMR techniques. Neurolobatin A (1) and B (2) are unusual isomeric seco-germacranolide sesquiterpenes with a bicyclic acetal moiety, compounds 3 and 4 are unsaturated epoxy-germacranolide esters, and compound 5 is the first eudesmanolide isolated from the genus Neurolaena. The isolated compounds (1-5) were shown to have noteworthy antiproliferative activities against human tumor cell lines (A2780, A431, HeLa, and MCF7). The anti-inflammatory effects of 1-5, evaluated in vitro using LPS- and TNF-α-induced IL-8 expression inhibitory assays, revealed that all these compounds strongly down-regulated the LPS-induced production of IL-8 protein, with neurolobatin B (2) and 3-epi-desacetylisovaleroylheliangine (4) being the most effective. © 2014 The American Chemical Society and American Society of Pharmacognosy. Source


Konczol A.,Compound Profiling Laboratory | Muller J.,Compound Profiling Laboratory | Muller J.,Budapest University of Technology and Economics | Foldes E.,Budapest University of Technology and Economics | And 4 more authors.
Journal of Natural Products | Year: 2013

While numerous natural products (NPs) possess activity on central nervous system (CNS) targets, there has been no analytical approach to effectively identify compounds with high brain penetration potential in complex mixtures at the early stage of drug discovery. To overcome this issue, the performance of an in vitro parallel artificial membrane permeability assay for the blood-brain barrier (PAMPA-BBB) for natural products and for plant extracts has been validated and characterized. It was found that the PAMPA-BBB assay preserves its predictive power in the case of natural products and provides high phytochemical selectivity, which enables its use as a unique filtering tool in terms of selecting brain-penetrable compounds from plant extracts. Moreover, the present study has demonstrated that simple modifications in the assay design allow the direct use of PAMPA-BBB filtered samples in a dereplication process, as performed by NMR and LC-MS. The applicability of this procedure was demonstrated using extracts prepared from Tanacetum parthenium, Vinca major, Salvia officinalis, and Corydalis cava, representing different types of chemical diversity and complexity. Thus, the proposed protocol represents a potentially valuable strategy in the NP-based CNS drug discovery environment with a high-throughput screening platform. © 2013 The American Chemical Society and American Society of Pharmacognosy. Source


Marosi A.,Semmelweis University | Szalay Z.,Drug Polymorphism Research | Beni S.,Semmelweis University | Szakacs Z.,Spectroscopic Research | And 4 more authors.
Analytical and Bioanalytical Chemistry | Year: 2012

Multinuclear one (1D-) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopic investigations of famotidine, the most potent and widely used histamine H 2-receptor antagonist, were carried out in dimethyl sulfoxide-d 6 (DMSO-d 6) and water. Previous NMR assignments were either incomplete or full assignment was based only on 1D spectra and quantum-chemical calculations. Our work revealed several literature misassignments of the 1H, 13C, and 15N NMR signals and clarified the acid-base properties of the compound at the site-specific level. The erroneous assignment of Baranska et al. (J. Mol. Struct. 2001, 563) probably originates from an incorrect hypothesis about the major conformation of famotidine in DMSO-d 6. A folded conformation similar to that observed in the solid-state was also assumed in solution, stabilized by an intramolecular hydrogen bond involving one of the sulphonamide NH 2 protons and the thiazole nitrogen. Our detailed 1D and 2D NMR experiments enabled complete ab initio 1H, 13C, and 15N assignments and disproved the existence of the sulphonamide NH hydrogen bond in the major conformer. Rather, the molecule is predominantly present in an extended conformation in DMSO-d 6. The aqueous acid-base properties of famotidine were studied by 1D 1H- and 2D 1H/ 13C heteronuclear multiple-bond correlation (HMBC) NMR-pH titrations. The experiments identified its basic centers including a new protonation step at highly acidic conditions, which was also confirmed by titrations and quantum-chemical calculations on a model compound, 2-[4-(sulfanylmethyl)-1,3-thiazol-2-yl]guanidine. Famotidine is now proved to have four protonation steps in the following basicity order: the sulfonamidate anion protonates at pH∈=∈11.3, followed by the protonation of the guanidine group at pH∈=∈6.8, whereas, in strong acidic solutions, two overlapping protonation processes occur involving the amidine and thiazole moieties. © 2011 Springer-Verlag. Source


Veszelka S.,Hungarian Academy of Sciences | Toth A.E.,Hungarian Academy of Sciences | Walter F.,Hungarian Academy of Sciences | Kittel A.,Hungarian Academy of Sciences | And 8 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2012

An accurate means of predicting blood-brain barrier (BBB) penetration and blood-brain partitioning of NCEs (new chemical entities) would fulfill a major need in pharmaceutical research. Currently, an industry-standard BBB drug penetration model is not available. Primary brain capillary endothelial cells, optionally co-cultured with astrocytes and/or pericytes, are the most valued models of BBB. For routine use, establishing and maintaining a co-culture system is too costly and labor intensive. Alternatively, non-cerebral cell lines such as MDCK-MDR1 are used, and most recently, the suitability of native and modified Caco-2 for predicting brain penetration has also come under investigation. This study provides comparative data on the morphology and functionality of the high integrity brain capillary endothelial BBB model (EPA: triple culture of brain capillary endothelial cells with pericytes and astrocytes) and the epithelial cell-based (native Caco-2, high P-glycoprotein expressing vinblastine-treated VB-Caco-2 and MDCK-MDR1) surrogate BBB models. Using a panel of 10 compounds VB-Caco-2 and MDCK-MDR1 cell lines show restrictive paracellular pathway and BBB-like selective passive permeability that makes them comparable to the rat brain BBB model, which gave correlation with the highest r2 value with in vivo permeability data. In bidirectional assay, the VB-Caco-2 and the MDCK-MDR1 models identified more P-glycoprotein drug substrates than the rat brain BBB model. While the complexity and predictive value of the BBB model is the highest, for the screening of NCEs to determine whether they are efflux substrates or not, the VB-Caco-2 and the MDCK-MDR1 models may provide a simple and inexpensive tool. © 2012 Elsevier B.V. All rights reserved. Source

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