Abstract
In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aβ aggregation and antioxidant activity.
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•A series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed and synthesized.•The inhibiting activity of synthesized compounds on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) showed submicromolar to micromolar activity.•AChE selectivity of most promising compound was ∼12 fold more potent than BuChE.•Inhibition of Aβ1-42 and AChE-induced Aβ1-42 aggregation of synthesized compounds were more effective than curcumin.•Oxygen radical absorbance capacity of synthesized compounds was superior to that of Trolox.