Abstract
One of well-established biological activities for chalcone derivatives is as acetylcholinesterase inhibitors, which can be developed for the therapy of Alzheimer’s disease. Assisted byretrospectively validated structure-based virtual screening (SBVS) protocol to identify potent acetylcholinesterase inhibitors, 80chalcone derivatives were designed and virtually screened. The F -measure value as the parameter of the predictive ability of the SBVS protocol developed in the research presented in this article was 0.413, which was considerably better than the original SBVS protocol ( F -measure = 0.226). Among the screened chalcone derivatives two were selected as potential lead compounds to designpotent inhibitors for acetylcholinesterase: 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one( 3k ) and 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxyphenyl)prop-2-en-1-one ( 4k ).
Highlights
Alzheimer’s disease (AD), a progressive brain disorder, is a neurodegenerative disease which becomes symptomatic after brain changing happened over the years (Aggarwal et al, 2015)
The research presented in this paper was aimed to design chalcone derivatives as potent AChE inhibitors by utilizing retrospectively validated structure-based virtual screening (SBVS) protocols constructed by employing PLANTS1.2 as the molecular docking software (Korb et al, 2009, 2007)and PyPLIFas the Protein-Ligand Interaction Fingerprints (PLIF) identification software for re-scoring (Radifar et al, 2013a; Radifar et al, 2013b)
Aimed to initiate the discovery and development of potent AChE inhibitors, this research constructed and optimized the predictive ability of SBVS protocol to identify potent AChE inhibitors and employed the best protocol to select best potential inhibitors from 80 chalcone derivatives presented in Table I as lead compounds
Summary
Alzheimer’s disease (AD), a progressive brain disorder, is a neurodegenerative disease which becomes symptomatic after brain changing happened over the years (Aggarwal et al, 2015). The deficiency of the brain neurotransmitter acetylcholine (ACh) is often associated with pathogenesis of AD (Tabet, 2006). Acetylcholine plays important roles in the nervous system such as increasing neurotransmitter release, supporting synaptic transmission, inducing synaptic plasticity, and coordinating firing of groups of neurons (Picciotto et al, 2012; Tsuda, 2012). The hydrolysis of ACh into choline and acetic acid, a reaction needed to allow the returning of cholinergic neuron to the resting state, was catalyzed by a family of enzymes called cholinesterase (Colovic et al, 2013). Acetylcholinesterase (AChE), one of cholinesterase types found in many types of conducting tissue, is a highly possible therapeutic target of Alzheimer disease (Mehta et al, 2012)
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