Interaction of (benzylidene-hydrazono)-1,4-dihydropyridines with β-amyloid, acetylcholine, and butyrylcholine esterases
Makaleler > Tam Makale · 2010
Yazarlar: Vildan ALPTÜZÜN, Michaela Prinz, Verena Hoerr, Josef Scheiber, Krzysztof Radacki, Adyary Fallarero, Pia Vuorela, Bernd Engels, Holger Braunschweig, Ercin ERCİYAS, Ulrike Holzgrabe
Bioorganic & Medicinal Chemistry, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2010, cilt 18, ss 2049-2059
DOI: 10.1016/j.bmc.2010.01.002
Özet
Approved drugs for the treatment of Alzheimer's disease belong to the group of inhibitors of the acetylcholinesterase (AChE) and NMDA receptor inhibitors. However none of the drugs is able to combat or reverse the progression of the disease. Thus, the recently reported promising multitarget-directed molecule approach was applied here. Using the lead compound DUO3, which was found to be a potent inhibitor of the AChE and butyrylcholinesterase (BuChE) as well as an inhibitor of the formation of the amyloid ( Ab) plaque, new non-permanently positively charged derivatives were synthesized and biologically characterized. In contrast to DUO3 the new bisphenyl-substituted pyridinylidene hydrazones 5 are appropriate to cross the blood-brain barrier due to their pK(a) values and lipophilicity, and to inhibit both the AChE and BuChE. More important some of the pyridinylidene hydrazones inhibit the Ab fibril formation completely and destruct the already formed fibrils significantly. (C) 2010 Elsevier Ltd. All rights reserved.