Microwave assisted synthesis of novel hybrid tacrine-sulfonamide derivatives and investigation of their antioxidant and anticholinesterase activities.
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=0.009μM. This value is 220-fold greater than that of galantamine (IC50=2.054μM) and 6-fold greater than tacrine (IC50=0.055μM). VIIIf displayed the strongest inhibition of BuChE (IC50=2.250μM), which is close to donepezil (IC50=2.680μM) and 8-fold greater than that of galantamine (IC50=18.130μM) 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±2.310μM) showed significantly better ABTS cation radical scavenging ability than all of the new synthesized compounds.
Chemistry Department, Faculty of Arts and Science, Dumlupınar University, 43100 Kütahya, Turkey.
Ramazan
R
Ulus
Department of Pharmaceutical and Analytical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Istanbul, Turkey.
Belma
B
Zengin Kurt
Department of Pharmaceutical and Analytical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Istanbul, Turkey.
Isil
I
Gazioğlu
Biochemistry Department, Faculty of Arts and Science, Dumlupınar University, 43100 Kütahya, Turkey. Electronic address: muharrem.kaya@dpu.edu.tr.
Muharrem
M
Kaya
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry; D001713:Biphenyl Compounds / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus; D005609:Free Radicals / Q000737:chemistry; D006736:Horses; D006801:Humans; D008872:Microwaves; D010851:Picrates / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013451:Sulfonic Acids / Q000737:chemistry; D013619:Tacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
D000975:Antioxidants; D052160:Benzothiazoles; D001713:Biphenyl Compounds; D002800:Cholinesterase Inhibitors; D005609:Free Radicals; D010851:Picrates; D013449:Sulfonamides; D013451:Sulfonic Acids; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D013619:Tacrine; C004931:1,1-diphenyl-2-picrylhydrazyl; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
AChE; Antioxidant; BuChE; Chromene; Sulfonamide; Tacrine