title: Synthesis of Novel Benzothiazole-Piperazine Derivatives and Their Biological Evaluation as Acetylcholinesterase Inhibitors and Cytotoxic Agents.
abstract: A new series of benzothiazole-piperazine derivatives was synthesized and a complete chemical characterization of the novel compounds was provided. In vitro cytotoxic activities were screened against colorectal (HCT-116), breast (MCF-7) and hepatocellular (Huh7) cancer cell lines by Sulforhodamine B assay.
  
  
  
  All compounds showed cytotoxic activity against hepatocellular (Huh7) and breast (MCF-7) cancer cell lines. Dihalo substituted benzylpiperazine derivatives (2a, 2e) had the highest cytotoxic activities in all the tested cell lines. In addition, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of synthesized compounds were investigated by in vitro Ellman's method. Compound 2j led to moderate and selective inhibition against AChE. Docking study was utilized to understand the binding mode of compound 2j in comparision with donepezil on AChE. The other tested compounds showed weak or no inhibition against AChE as promising anticancer agents.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, 34755, Kayisdagi, Istanbul. Turkey.
authors.forename: Enise Ece
authors.initials: EE
authors.lastname: Gurdal
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, 34755, Kayisdagi, Istanbul. Turkey.
authors.forename: Bengisu
authors.initials: B
authors.lastname: Turgutalp
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, Famagusta. Cyprus.
authors.forename: Hayrettin Ozan
authors.initials: HO
authors.lastname: Gulcan
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, Famagusta. Cyprus.
authors.forename: Tugba
authors.initials: T
authors.lastname: Ercetin
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, Famagusta. Cyprus.
authors.forename: Mustafa Fethi
authors.initials: MF
authors.lastname: Sahin
authors.affiliation: Bioinformatics Department, Graduate School of Informatics, Middle East Technical University, Ankara. Turkey.
authors.forename: Irem
authors.initials: I
authors.lastname: Durmaz
authors.affiliation: Bioinformatics Department, Graduate School of Informatics, Middle East Technical University, Ankara. Turkey.
authors.forename: Rengul Cetin
authors.initials: RC
authors.lastname: Atalay
authors.affiliation: Martin-Luther- Universität Halle-Wittenberg, Institute of Pharmacy, Medicinal Chemistry Department, Halle (Saale). Germany.
authors.forename: Quoc Dat
authors.initials: QD
authors.lastname: Nguyen
authors.affiliation: Martin-Luther- Universität Halle-Wittenberg, Institute of Pharmacy, Medicinal Chemistry Department, Halle (Saale). Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, 34755, Kayisdagi, Istanbul. Turkey.
authors.forename: Mine
authors.initials: M
authors.lastname: Yarim
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects*; D052160:Benzothiazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000077265:Donepezil / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D000077489:Piperazine / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods; D013329:Structure-Activity Relationship
chemical_list: D052160:Benzothiazoles; D002800:Cholinesterase Inhibitors; D000077489:Piperazine; D000077265:Donepezil; D000110:Acetylcholinesterase; C005465:benzothiazole
keywords: Acetylcholinesterase; Ellman's method; Sulforhodamine B; benzothiazole; cytotoxicity; docking; piperazine