Inhibition, ADME and structure based modification of IAA and IBA against acetylcholinesterase: an attempt towards new drug development for Alzheimer's disease

Indole derived compounds have gained considerable attention in the pharmaceutical industry due to their pharmacological and structural properties. Indole-3-acetic acid (IAA) and indole 3-butyric acid (IBA) are two indole derivatives used in plant tissue culture experiments. They are plant growth regulators generally known as auxins. Since acetylcholinesterase (AChE) inhibitors prevent the hydrolysis of neurotransmitter acetylcholine, they may be suitable for the treatment of Alzheimer's disease. The IC50 and atomic level interaction of IAA and IBA against AChE were determined by enzyme inhibition and molecular docking studies. In order to improve central nervous system activity and blood brain permeability, in silico modification of the structure has been carried out. The modified compounds were screened by docking against AChE and butyrylcholinesterase (BChE). Based on the docking studies, four new derivatives have been identified for drug development against neurodegenerative disorders such as Alzheimer's disease.