title: Design, synthesis, and AChE inhibitory activity of new benzothiazole-piperazines.
abstract: In the current study, 14 new benzothiazole-piperazine compounds were designed to meet the structural requirements of acetylcholine esterase (AChE) inhibitors. The target compounds were synthesised in three steps. Structures of the newly synthesised compounds (7-20) were confirmed using IR,1H NMR,13C NMR, and HRMS methods. The inhibitory potential of the compounds on AChE (E.C.3.1.1.7, from electric eel) was then investigated. Among the compounds, 19 and 20 showed very good activity on AChE enzyme. Kinetics studies were performed to observe the effects of the most active compounds on the substrate-enzyme relationship. Cytotoxicity studies, genotoxicity studies, and theoretical calculation of pharmacokinetics properties were also carried out. The compounds 19 and 20 were found to be nontoxic in both of the toxicity assays. A good pharmacokinetics profile was predicted for the synthesised compounds. Molecular docking studies were performed for the most active compounds, 19 and 20, and interaction modes with enzyme active sites were determined. Docking studies indicated a strong interaction between the active sites of AChE enzyme and the analysed compounds.
authors: Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Ümide
authors: Ü
authors: Demir Özkay
authors: Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Özgür Devrim
authors: ÖD
authors: Can
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Begüm Nurpelin
authors: BN
authors: Sağlık
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Ulviye
authors: U
authors: Acar Çevik
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Serkan
authors: S
authors: Levent
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. Electronic address: yozkay@anadolu.edu.tr.
authors: Yusuf
authors: Y
authors: Özkay
authors: Department of Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Sinem
authors: S
authors: Ilgın
authors: Department of Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Özlem
authors: Ö
authors: Atlı
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004593:Electrophorus; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D041681:NIH 3T3 Cells; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D002800:Cholinesterase Inhibitors; D010879:Piperazines; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Alzheimer disease; Benzothiazole; Docking; Piperazine