Abstract

Acetylcholinesterase (AChE), plays a key role as an essential enzyme in memory and cognition process trough the hydrolysis of neurotransmitter acetylcholine. Although the physiological role of AChE in neural transmission is well known, its role as harmaceutical target for the treatment of Alzheimer’s disease (AD) is still matter of extensive research. It has been elucidated that cholinergic deficiency is associated with AD. Therefore, one of the major therapeutic strategies is to inhibit the biological activity of AChE, increasing the acetylcholine level in the brain. However, one of the major limitations of up-regulating AChE activity through acetycholinesterase inhibition is that repeated doses of acetylcholinesterase inhibitor (AChEi) lead to the development of tolerance. Despite its limited success, AChEi remains as the only approved treatment by Food and Drug Administration (FDA) for AD. This scenario has led to strong efforts to discover new AChEi from a vast number of plant species, which can provide new bioactive compounds for control strategies in AD. Thus, natural alkaloids have been shown to be potent AChEi. However, the process of AChEi-based drug development is challenging, time consuming, expensive, and requires consideration of many aspects (eg. chemical structure, identification and biological assay). Therefore, the computer- based methods are becoming increasingly important as they complement laboratory experiments in studying the structure and function of biomolecules. Specifically, molecular docking has been highlighted as a frequently used tool in structure-based drug discovery. Although early efforts were hindered by limited possibilities in computational resources, the recent advance in high performance computing with virtual screening methods has become drug discovery more efficient. Therefore, the objective of this review is to summarize the usefulness of molecular docking related to alkaloid research as well as new approaches for alkaloid discovery using AChE as targets.