Evaluation of novel multifunctional organoselenium compounds as potential cholinesterase inhibitors against Alzheimer's disease

Acetylcholinesterase (AChE) inhibitors are of widespread interest to the pharmaceutical communities. Herein, 34 organoselenium compounds were synthesized in good yields and evaluated for their AChE inhibition and glutathione peroxidase (GPX) like activities. The highest AChE inhibition efficiency was observed for the tetrazole-based selenocyanate 12 (64%), selenonaphthoquinone-based urea 39 (63.1%), tetrazole-based diselenide 25 (59.4%), selenocyanate-based urea 18 (58.4%) and selenobenzoquinone-based urea 36 (57.9%). On the other hand, the GPX highest activity was recorded for the pseudopeptide-based diselenides 21 (48.5 mu M/min). Fair-moderate activities were observed for the pseudopeptide-based diselenides 22 (24.4 mu M/min) and 24 (18.3 mu M/min). Docking studies for 8, 12, 18, 25, and 39 compounds in AChE active site showed their similar orientation to Donepezil at the catalytic site (CAS) and the peripheral anionic site (PAS), a result that supports their inhibitory effect. This study presents a new set of synthetic organoselenium compounds with a significant inhibitory effect against AChE.

Automated summary

This study synthesized a new set of organic selenium compounds with significant inhibitory effect against AChE, and evaluated their inhibition activity on AChE and GPX. Some compounds showed high AChE inhibition efficiency and exhibited similar orientation to Donepezil at the AChE active site.