Published January 1, 2010
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Interaction of (benzylidene-hydrazono)-1,4-dihydropyridines with beta-amyloid, acetylcholine, and butyrylcholine esterases
Creators
- 1. Ege Univ, Fac Pharm, Bornova, Turkey
- 2. Univ Wurzburg, Inst Pharm & Food Chem, D-97074 Wurzburg, Germany
- 3. Univ Wurzburg, Inst Inorgan Chem, D-97074 Wurzburg, Germany
- 4. Abo Akad Univ BioCity, Div Pharm, Fac Math & Nat Sci, FI-20520 Turku, Finland
- 5. Univ Wurzburg, Inst Organ Chem, D-8700 Wurzburg, Germany
Description
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.
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