Acetylcholinesterase inhibitors: Modeling potential candidates

• Published in: International journal of quantum chemistry 2013-05, Vol.113 (10), p.1461-1466
• Main Authors: Kiametis, Alessandra S., Martins, João B. L., Romeiro, Luiz A. S., Gargano, Ricardo
• Format: Article
• Language: English
• Subjects: acetylcholinesterase enzyme; Alzheimer's disease; Chemistry; donepezil drug; electronic structure; Physical chemistry; principal component analysis; Quantum physics
• ISSN: 0020-7608; 1097-461X
• DOI: 10.1002/qua.24341

Alzheimer's disease is the leading cause of dementia for elderly people. The main active therapeutic is supported on the increased levels of acetylcholine in the synaptic cleft, based on reversible inhibition of the acetylcholinesterase (AChE) enzyme. This article aims to propose possible inhibitor candidates for AChE, designed from nonisoprenoid lipids of cashew (Anacardium occidentale), and based on several electronic properties. These electronic properties were obtained through B3LYP/6‐311+G(2d,p) calculation level. Principal component analysis reveals that from the set of studied molecular structures a small group is correlated with donepezil, a drug with known biological activity. © 2012 Wiley Periodicals, Inc. Increased levels of acetylcholine by reversible inhibition of acetilcolinesterase (AChE) are considered to improve the cognitive profile of Alzheimer's disease patients. This work presents some candidates for AChE inhibitors, selected considering possible ligand–receptor interactions, and their molecular descriptors. Among these candidates calculations identify a derivate of donepezil, a bioactive drug.