Design and Development of Cholinesterase Dual Inhibitors towards Alzheimer's Disease Treatment: A Focus on Recent Contributions from Computational and Theoretical Perspective

In recent times, review topics on Alzheimer's disease (AD) have received massive attention, especially on drug design and development of potent inhibitors targeting specific pathway(s) of this multifaceted disease. Drug design and development through the use of computer has taken an intriguing dimension over the last two decades, and AD drug design is not an exception. Computational approaches have found usage in identifying potentially active molecules targeting specific enzyme or gene in the pathological pathway of a disease such as AD. Herein, we present an overview of research contributions over the last ten years from different authors who had used computational approaches to explore potent dual inhibitors of the cholinesterase enzymes linked with AD pathogenesis. We gave an introductory background of the disease, highlight challenges of in silico approach to drug design, and discuss its pros and cons. The overview also covers previously reported review works which are related to the topic. We proposed that continued research efforts to unravel more effective dual acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors through computational tools could plausibly be a successful approach to AD cure. Computational researchers should leverage on the available cost‐effective resources to identify lead compounds and work in collaboration with experimental personnel to push their discovery forward.