Design of potent inhibitors of acetylcholinesterase using morin as the starting compound

Abstract

Inhibition of acetylcholinesterase (AChE) is a promising treatment strategy for Alzheimer's disease (AD). Oxidative stress, inflammation and accumulation of metal ions at sites of neurodegeneration have been observed in association with AD. Flavonoids are well known for their action against inflammation and oxidative stress. Hence, they can be used for treating diseases such as AD, cancer, atherosclerosis and Parkinson's disease. Flavonols such as quercetin, myricetin, galangin, fisetin and kaempferol have been reported as inhibitors of AChE. In the present work, the enzyme inhibitory properties of morin, a flavonol, has been tested against AChE. The binding pattern of morin and 12 other flavonols at the active site of human AChE has been analyzed using molecular modeling and docking methods. In order to enhance the binding affinity of AChE for morin, in silico structural modification of the compound was carried out. The structural elements responsible for its biological functions were retained during the modification. Some of the derivatives possessed better binding energies than morin and hence they could be used as drug lead compound for the treatment of AD.