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Yao Chen Jie Zhu Jun Mo Hongyu Yang Xueyang Jiang Hongzhi Lin 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):290-302
Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer’s disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure–activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50?=?10.2?±?1.2, 16.5?±?1.7, and 15.3?±?1.8?nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD. 相似文献
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Kuo Huang Ling Bai Jiun Chen Yun Wen Peng Shih Chong Tsai Fu Chuo Peng Chung Kuang Yang 《Mycotoxin Research》1987,3(2):58-64
The chemical reaction of cleavaging territrem B to give 3,4,5-trimethoxy benzoic acid by alkaline hydrogen peroxide was investigated. The method was applied for confirmation of the chemical structure of the aromatic moiety of territrem A, A’, B, and B’. The physicochemical properties of the aromatic cleavage product of territrem Aindicated the structure as 3,4-methylendioxy, 5-methoxy benzoic acid (or 4-methoxy, 6-carboxy, 1, 3-benzodioxole). The experiment also gave the evidences that territrem A and A’, on the other hand territrem B and B’ have the identical aromatic moieties on their structures. 相似文献
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本文评价了六种选矿药剂对藻类的毒性效应,它们对斜生栅藻的毒性大小排列顺序是:二号油>Fu>0145>Yx>MPA>S-808,96h-EC_(50)值分别为41.2,50.1,82.0,177.8,198.2和900ppm。六种选矿药剂对藻类毒性最大的是二号油,毒性最小的是S-808。对藻类细胞形态的观察结果表明,0145对藻类的细胞形态有轻度的致畸效应,在其它五种药剂的培养物中,均未发现畸变细胞。在室温下存放10d后MPA,0145和二号油,毒性明显下降,其下降速率的顺序是:MPA>0145>二号油。藻类对S-808具有净化脱色作用,100ppm浓度的S-808溶液经藻类作用32d后,其色度可减少48%,作用62d和93d,色度分别降低54%和58%。0145抑制藻类的光合放氧,经50,100和200ppm浓度的0145处理4h后,与对照相比,藻类的光合放氧速率分别下降15、34和36%。 相似文献
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Manju Basu Shu-Ai Weng Hongyu Tang Farhat Khan Federica Rossi Subhash Basu 《Glycoconjugate journal》1996,13(3):423-432
The galactosyltransferase, GalT-4, which catalyses the biosynthesisin vitro of neolactotetraosylceramide, nLcOse4Cer (Gal1-4GleNAc1-3Gal1-4Glc-Cer) from lactotriaosylceramide, LcOse3Cer (GlcNAc1-3Gal1-4Glc-Cer), and UDP-galactose has been purified 107 500-fold from a mineral oil induced mouse T-lyphoma P-1798, using affinity columns. The purified enzyme is partially stabilized in the presence of phospholipid liposomes. Two closely migrating protein bands of apparent molecular weights 56 kDa and 63 kDa were observed after sodium dodecyl sulfate polyacrylamide gel electrophoresis of highly purified mouse GalT-4. These two protein bands, when subjected to limited proteolysis, resulted in three peptides with identical mobilities indicating amino acid sequence identity between the proteins. Both protein bands from P-1798 gave a positive immunostain when tested with polyclonal antibody against bovine lactose synthetase (UDP-Gal:Glc 4-galactosyltransferase) following Western blot analysis on nitrocellulose paper. The enzyme has a pH optimum between 6.5 and 7.0 and like all other galactosyltransferases, GalT-4 has absolute requirements for divalent cation (Mn2+). TheK
m values for the substrate LcOse3Cer and donor UDP-galactose are 110 and 250 µm, respectively. Substrate competition studies with LcOse3Cer and either asialo-agalacto-1-acid glycoprotein orN-acetylglucosamine revealed that these reactions might be catalysed by the same protein. The only other glycolipid which showed acceptor activity toward the purified GalT-4 was iLcOse5Cer (GlcNAc1-1-3Gal1-4Lc3), the precursor for polylactosamine antigens. However, competition studies with these two active substrates using the most purified enzyme fraction, revealed that these two reactions might be catalysed by two different proteins since the experimental values were closer to the theoretical values calculated for two enzymes. Interestingly however, it seems that the GalT-4 from P-1798 has an absolute requirement for anN-acetylglucosamine residue in the substrate since the lyso-derivative (GlcNH21-3Gal1-4Glc-sphingosine) of the acceptor glycolipid LcOse3Cer is completely inactive as substrate while theK
m andV
max of the reacetylated substrate (GlcNac1-3Gal1-4Glc-acetylsphingosine) was comparable with LcOse3Cer. Autoradiography of the radioactive product formed by purified P-1798 GalT-4 confirmed the presence of nLcOse4Cer, as the product cochromatographed with authentic glycolipid. The monoclonal antibody IB-2, specific for nLcOse4Cer, also produced a positive immunostained band on TLC as well as giving a positive ELISA when tested with radioactive product obtained using a highly purified enzyme from mouse P-1798 T-lymphoma.Abbreviations EDTA
ethylenediamine tetraacetate
- ME
-mercaptoethanol
- PEG
polyethylene glycol
- PBS
phosphate buffered saline
- Suc
sucrose
- Mn2+
manganese
- Gal
galactose
- GlcNAc
N-acetylglucosamine
- UDP-Gal
Uridine diphosphate galactose
- Ab
antibody
- SDS
sodium dodecyl sulphate
- PAGE
polyacrylamide gel electrophoresis
- ECB
embryonic chicken brain
- Cer
ceramide
- nLc4 or NlcOse4Cer
Gal1-4GleNac1-3Gal1-4Glc-Cer, neoLactotetraosylceramide
- Lc3 or LcOse3Cer
GlcNac1-3Gal1-4Glc-Cer, lactotriaosylceramide
- iLc5
iLcOse5Cer, GlcNAc1-3nLcOse4Cer
- nLc6
nLcOse6Cer, Gal1-4iLcOse5Cer
- SA–Gal–1AGP
asialo-agalacto1-acid glycoprotein
- TLC
thin layer chromatography 相似文献
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华南胡椒化学成分的研究 总被引:1,自引:0,他引:1
从胡椒科植物华南胡椒(Piper austrosinense C.DC.)中分离出七个成分,经光谱分析和理化常数测定,分别鉴定为N-isobutyl-3(3',4'-methylenedioxy-5'-methoxyphenyl)-2E-trimonoienamide(I)、N-isobutyl-7(3',4'-metylenedioxyphenyl)-2E,4E-heptadienamide(Ⅱ 相似文献
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本文设计一种由胶原和高分子聚合物组成的新型生物一人工复合血管。其研制过程是将包绕有聚酯网的硅胶棒埋入羊的皮下组织,再将形成的经聚酯网为支架的胶原管经醛化处理。作者通过肉眼和SEM观察提出了研制生物——人工复合血管的要点:聚酯网网孔要合适,其与硅胶棒的间隙要恰当,理化处理方法更要选择好。 相似文献