Synthesis of indole derivatives as Alzheimer inhibitors and their molecular docking study

Acetylcholinesterase prevails in the healthy brain, with butyrylcholinesterase reflected to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity gradually increases in patients with (AD), while AChE activity remains unaffected or decays. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioural, and global functioning characteristic of AD. Current study described the synthesis of indole-based sulfonamide derivatives (1-23) and their biological activity. Synthesis of these scaffolds were achieved by mixing chloro-substituted indole bearing amine group with various substituted benzene sulfonyl chloride in pyridine, under refluxed condition to obtained desired products. All products were then evaluated for AchE and BuchE inhibitory potential compare with positive Donepezil as standard drug for both AchE and BchE having IC50 = 0.016 +/- 0.12 and 0.30 +/- 0.010 mu M respectively. In this regard analog 9 was found potent having IC50 value 0.15 +/- 0.050 mu M and 0.20 +/- 0.10 for both AchE and BuChE respectively. All other derivatives also found with better potential. All compounds were characterized by various techniques such as H-1, C-13-NMR and HREI-MS. In addition, biological activity was maintained to explore the bioactive nature of scaffolds and their protein-ligand interaction (PLI) was checked through molecular docking study.Communicated by Ramaswamy H. Sarma

Automated summary

Acetylcholinesterase and butyrylcholinesterase are both valid therapeutic targets for ameliorating the cholinergic deficit in Alzheimer's disease. This study describes the synthesis of indole-based sulfonamide derivatives and their inhibitory activity against the enzymes. Compound 9 showed strong potential as an inhibitor.