Computer-aided design of chalcone derivatives as lead compounds targeting acetylcholinesterase

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 by retrospectively validated structure-based virtual screening (SBVS) protocol to identify potent acetylcholinesterase inhibitors, 80 chalcone 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 design potent inhibitors for acetylcholinesterase: 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxy-3-methoxy-phenyl)prop-2-en-1-one(3k) and 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxyphenyl)prop-2-en-1-one (4k).