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Ivana Šagud Nikolina Maček Hrvat Ana Grgičević Tena Čadež Josipa Hodak Milena Dragojević 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):460-467
Abstract The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC50 in µM range) and AChE poorly (IC50?100?µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.
- HIGHLIGHTS
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Series of oxazole benzylamines were designed and synthesised
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The tested compounds showed binding selectivity for BChE
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Naphthoxazoles were more potent AChE inhibitors
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Milena Rychnovská-Soudková 《Biologia Plantarum》1963,5(2):175-180
Jedním z kritérií pro posuzování odolnosti rostiin v??i suchu je jejich schopnost sná?et vodní deficit ani? nastanou irreversibilní změny v jejich pletivech. Tato schopnost byla zkoumána metodikou, popsanou v p?edlo?ené práci. Listy některých xerothermních trav (druhy roduStipa, Melica atd.) vysýchaly za p?esně definovaných pokusných podmínek tak, ?e dosáhly r?zně odstupňovaného vodního deficitu. Potom byly roz?ezány na segmenty a ve speciálním ráme?ku dosycovány vodou. P?vodní deficit i jeho vyronání bylo sledvváno váhově. Výsledné hodnoty byly znázorněny graficky. Zatímco ztráta vody z list? během vysýchání probíhala v některých p?ípadech lineárně, k?ivka dosycování ukazovala charakteristický zlom, který indikoval, jak dalece byla ztráta vody nahraditelná, a kdy do?lo ji? k irreversibilním změnám. Ukázalo se, ?e ze studované série rostlin druhy typicky kontinentální mají schopnost doplňovat svou zásobu vody ad integrum i p?i zna?ném vodním deficitu. Rostliny s areálem spí? oceánického charakteru tuto schopnost nemají. Je pravděpodobné, ?e i tato vlastnost bude směrodatná p?i výkladu kausální fytogeografie. 相似文献
76.
Aminopeptidase activity is asymmetrically distributed in selected zones of rat brain 总被引:1,自引:0,他引:1
Levels of soluble aminopeptidase (AP), measured as arylamidase activity using L-Leucine-2-Naphthylamide (Leu-2-NA) as substrate, were determined in the soluble fraction of eleven zones of rat brain. Results showed that AP activity is asymmetrically distributed in frontal cortex and hypothalamus with both left sides having significantly higher levels of AP activity, respectively, than the right sides. Simultaneously, the activities of lactate dehydrogenase (LDH) and glutamate-oxalacetate aminotransferase (GOT) were measured in the same cerebral regions; no significant difference was recorded in these activities between either side of the rat brain in any of the zones studied. Provided that aminopeptidases are involved in the degradation of some endogenously released neuropeptides, the results suggest a new mode of expression of cerebral lateralization. 相似文献
77.
Mitochondrial DNA of pre‐last glacial maximum red deer from NW Spain suggests a more complex phylogeographical history for the species 下载免费PDF全文
Alba Rey‐Iglesia Aurora Grandal‐d'Anglade Paula F. Campos Anders Johannes Hansen 《Ecology and evolution》2017,7(24):10690-10700
The major climatic oscillations that characterized the Quaternary had a great influence on the evolution and distribution of several species. During cold periods, the distribution of temperate‐adapted species became fragmented with many surviving in southern refugia (Iberian, Italian, and Balkan Peninsulas). Red deer was one of the species that contracted its original range to southern refugia. Currently, two main lineages have been described for the species: western and eastern. We have analyzed fossils pre‐dating the last glacial maximum (LGM) from Liñares cave (NW Spain) that belongs to the peripheral range of the western clade, and fossils from the Danish Holocene belonging to the central part of the same clade. Phylogenetic analyses place our samples in the western clade. However, some specimens from Liñares represent an early split in the tree along with other pre‐LGM western samples from previous studies. Despite low bootstrap values in the Bayesian phylogenies, haplotype networks connect these foreign haplotypes to the eastern clade. We suggest a mixed phylogeographical model to explain this pattern with range expansions from the east during the expansion phase after the cold periods in marine isotope stage 3. We find slight isolation by distance in post‐LGM populations that could be a consequence of the recolonization from southern refugia after the LGM. 相似文献
78.
E. de Alba M. Rico M. A. Jimnez 《Protein science : a publication of the Protein Society》1997,6(12):2548-2560
A series of designed peptides has been analyzed by 1H-NMR spectroscopy in order to investigate the influence of cross-strand side-chain interactions in beta-hairpin formation. The peptides differ in the N-terminal residues of a previously designed linear decapeptide that folds in aqueous solution into two interconverting beta-hairpin conformations, one with a type I turn (beta-hairpin 4:4) and the other with a type I + G1 beta-bulge turn (beta-hairpin 3:5). Analysis of the conformational behavior of the peptides studied here demonstrates three favorable and two unfavorable cross-strand side-chain interactions for beta-hairpin formation. These results are in agreement with statistical data on side-chain interactions in protein beta-sheets. All the peptides in this study form significant populations of the beta-hairpin 3:5, but only some of them also adopt the beta-hairpin 4:4. The formation of beta-hairpin 4:4 requires the presence of at least two favorable cross-strand interactions, whereas beta-hairpin 3:5 seems to be less susceptible to side-chain interactions. A protein database analysis of beta-hairpins 3:5 and beta-hairpins 4:4 indicates that the former occur more frequently than the latter. In both peptides and proteins, beta-hairpins 3:5 have a larger right-handed twist than beta-hairpins 4:4, so that a factor contributing to the higher stability of beta-hairpin 3:5 relative to beta-hairpin 4:4 is due to an appropriate backbone conformation of the type I + G1 beta-bulge turn toward the right-handed twist usually observed in protein beta-sheets. In contrast, as suggested previously, backbone geometry of the type I turn is not adequate for the right-handed twist. Because analysis of buried hydrophobic surface areas on protein beta-hairpins reveals that beta-hairpins 3:5 bury more hydrophobic surface area than beta-hairpins 4:4, we suggest that the right-handed twist observed in beta-hairpin 3:5 allows a better packing of side chains and that this may also contribute to its higher intrinsic stability. 相似文献
79.
Alba?Blánquez Francisco?Guillén Juana?Rodríguez M.?Enriqueta?Arias Manuel?HernándezEmail author 《World journal of microbiology & biotechnology》2016,32(3):52
The presence of fluoroquinolone based antimicrobials in natural waters represents a significant emerging environmental problem. In this study the suitability of a novel alkaline bacterial laccase, SilA, from Streptomyces ipomoeae to degrade two key antimicrobials, Ciprofloxacin and Norfloxacin under alkaline conditions in the presence of natural mediators was assessed. Results showed that only the selected SilA-acetosyringone system was able to degrade more than 90 % of both fluoroquinolones. HPLC analysis of the degradation products obtained after enzyme treatment confirmed the disappearance of the antimicrobials and the mediator after 24 h. The time course of the degradation showed that during the first 4 h a 75 % of degradation of fluoroquinolones was detected while the mediator remained stable. A concomitant appearance of new chromatographic peaks derived from the fluoroquinolones and/or the mediator was detected. Moreover, toxicity assays demonstrated that the SilA-acetosyringone system was able to reduce the toxicity of Ciprofloxacin and Norfloxacin by 90 and 70 %, respectively. In conclusion, these findings support the suitability of a low cost and environmentally friendly strategy based on the SilA-acetosyringone system for a primary treatment of contaminated alkaline wastewaters with this type of emerging pollutants. 相似文献
80.
Yahya Sohrabi Helena Havelková Tetyana Kobets Matyá? ?íma Valeriya Volkova Igor Grekov Ta?ána Jaro?íková Iryna Kurey Jarmila Vojtí?ková Milena Svobodová Peter Demant Marie Lipoldová 《PLoS neglected tropical diseases》2013,7(7)