Current Bioinformatics

Yi-Ping Phoebe Chen
Department of Computer Science and Information Technology
La Trobe University


Review of Bioinformatics and Theoretical Studies of Acetylcholinesterase Inhibitors

Author(s): Francisco J. Prado-Prado, Manuel Escobar, Xerardo Garcia-Mera.


Alzheimer’s disease is a complex disease, and no single “magic bullet” is likely to prevent or cure it. That’s why current treatments focus on several different aspects, including helping people maintain mental function; managing behavioral symptoms; and slowing, delaying, or preventing the disease. Four medications are approved by the U.S. Food and Drug Administration to treat Alzheimer’s. Donepezil, rivastigmine, and galantamine are used to treat mild to moderate Alzheimer’s. Memantine is used to treat moderate to severe Alzheimer’s. These drugs work by regulating neurotransmitters (the chemicals that transmit messages between neurons). Treatment of AD by ACh precursors and cholinergic agonists was ineffective or caused severe side effects. ACh hydrolysis by AChE causes termination of cholinergic neurotransmission. Therefore, compounds which inhibit AChE might significantly increase the levels of ACh depleted in AD. However, these drugs don’t change the underlying disease process and may help only for a few months to a few years. In this sense, quantitative structure-activity relationships (QSAR) could play an important role in studying these AChE inhibitors. QSAR models are necessary in order to guide the AChE synthesis. In this work, we revised different bioinformatics and theoretical studies of Acetylcholinesterase inhibitors, design and computational studies for a very large and heterogeneous series of AChE inhibitors. First, we review 2D QSAR, 3D QSAR, CoMFA, CoMSIA and Docking and new theoretical methodology with different compound to find out the structural requirements. Next, we revised QSAR studies using method of Linear Discriminant Analysis (LDA) in order to understand the essential structural requirement for binding with receptor for AChE inhibitors.

Keywords: Acetylcholinesterase inhibitors, alzheimer's disease, COMFA, CoMSIA, molecular docking, QSAR, topological indices.

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Article Details

Year: 2013
Page: [496 - 510]
Pages: 15
DOI: 10.2174/1574893611308040012
Price: $58