Synthesis of Novel Benzothiazole-Piperazine Derivatives and Their Biological Evaluation as Acetylcholinesterase Inhibitors and Cytotoxic Agents

Title:Synthesis of Novel Benzothiazole-Piperazine Derivatives and Their Biological Evaluation as Acetylcholinesterase Inhibitors and Cytotoxic Agents

Volume: 17 Issue: 13

Author(s): Enise Ece Gurdal*, Bengisu Turgutalp, Hayrettin Ozan Gulcan, Tugba Ercetin, Mustafa Fethi Sahin, Irem Durmaz, Rengul Cetin Atalay, Quoc Dat Nguyen, Wolfgang Sippl and Mine Yarim

Affiliation:

• Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, 34755, Kayisdagi, Istanbul,Turkey

Keywords: Acetylcholinesterase, benzothiazole, cytotoxicity, docking, Ellman's method, piperazine, Sulforhodamine B.

Abstract: Objective and Method: 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.

Result and Discussion: 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.

Cite this article as:

Gurdal Ece Enise *, Turgutalp Bengisu , Gulcan Ozan Hayrettin , Ercetin Tugba, Sahin Fethi Mustafa, Durmaz Irem, Atalay Cetin Rengul , Nguyen Dat Quoc , Sippl Wolfgang and Yarim Mine, Synthesis of Novel Benzothiazole-Piperazine Derivatives and Their Biological Evaluation as Acetylcholinesterase Inhibitors and Cytotoxic Agents, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (13) . https://dx.doi.org/10.2174/1871520617666170412153604