A molecular dynamics study of components of the ginger (Zingiber officinale) extract inside human acetylcholinesterase: implications for Alzheimer disease

Abstract

Components of ginger (Zingiber officinale) extracts have been described as potential new drug candidates against Alzheimer disease (AD), able to interact with several molecular targets related to the AD treatment. However, there are very few theoretical studies in the literature on the possible mechanisms of action by which these compounds can work as potential anti-AD drugs. For this reason, we performed here docking, molecular dynamic simulations and mmpbsa calculations on four components of ginger extracts former reported as active inhibitors of human acetylcholinesterase (HssAChE), and compared our results to the known HssAChE inhibitor and commercial drug in use against AD, donepezil (DNP). Our findings points to two among the compounds studied: (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-on and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3- ethoxyphenyl) heptane-3,5-diyl diacetate, as promising new HssAChE inhibitors that could be as effective as DNP. We also mapped the binding of the studied compounds in the different binding pockets inside HssAChE and established the preferred interactions to be favored in the design of new and more efficient inhibitors.