Assessing Indole Derivative Molecules as Dual Acetylcholinesterase and Butyrylcholinesterase Inhibitors through In Vitro Inhibition and Molecular Modelling Studies

Alzheimer's Disease (AD) is the most common type of dementia that develops with age, threatens the quality of life, is increases in number around the world, and has no effective treatment. The most important therapeutic targets in drug development studies for the treatment of AD are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The inadequacy of existing AChE and BChE inhibitors in the treatment of AD has led to the need to identify new AChE/BChE inhibitors with fewer side effects. In this study, considering the pharmacological importance indole derivatives, inhibition effects of some indole derivative molecules (a-e) on AChE and BChE activity were investigated. IC50 values of a-e against AChE were found to be 0.480 µM, 1.682 µM, 0.916 µM, 1.093 µM, 0.340 µM, respectively. On the other hand, IC50 values of compounds a-e on BChE activity were determined as 2.18 µM, 4.49 µM, 2.28 µM, 6.36 µM, 1.940 µM, respectively. As a result, it was seen that indole derivatives (a-e) showed strong inhibition effect on both enzymes. Additionally, these inhibition results were supported by molecular modelling studies. As a conclusion, results of this study will contribute to studies on the synthesis of new indole-derived AChE and BChE inhibitors for the treatment of AD.