Ulus_2017_Bioorg.Chem_70_245

A novel series of tacrine derivatives containing sulfonamide group were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The result showed that all the synthesized tacrine-sulfonamides (VIIIa-o) exhibited inhibitory activity on both cholinesterases. VIIIg showed the highest inhibitory activity on AChE IC50=0.009muM. This value is 220-fold greater than that of galantamine (IC50=2.054muM) and 6-fold greater than tacrine (IC50=0.055muM). VIIIf displayed the strongest inhibition of BuChE (IC50=2.250muM), which is close to donepezil (IC50=2.680muM) and 8-fold greater than that of galantamine (IC50=18.130muM) Furthermore, all of the synthesized tacrine derivatives showed higher inhibition of BuChE than that of galantamine. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were investigated for the antioxidant activity. Among them, VIIIb (IC50=94.390+/-2.310muM) showed significantly better ABTS cation radical scavenging ability than all of the new synthesized compounds.