Novel Carbazoles as AChE Inhibitors: Synthesis, Molecular Docking and Dynamic Simulation Studies

Extensive exploration of N-substituted carbazole derivatives is underway as these compounds possess the therapeutic potential to address the neurological problems. The main aim of this study is to synthesize a series of N-substituted carbazole derivatives and investigate it’s in vitro and in silico ability to act as AChE inhibitors. The two-step synthesis was carried out that resulted in the development of novel carbazoles and then these were subsequently subjected to in vitro evaluation for acetylcholinesterase (AChE) inhibitory activity. Further to comprehend the binding interactions and establish a plausible binding mechanism, the molecular docking, molecular dynamics and computational ADME predictions were employed. Based on its IC50 value of 14.14 µM, -7.327 Kcal/mol binding energy and occupancy of the egg yolk region, which suggests the potential for brain entry, compound 4c was determined to be an active one among the synthesized compounds. Thus, compound 4c has the potential to be an AChE inhibitor and effective in treating Alzheimer’s disease.