Abstract
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 μM/min). Fair-moderate activities were observed for the pseudopeptide-based diselenides
22
(24.4 μM/min) and
24
(18.3 μM/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.