A benzothiazole/piperazine derivative with acetylcholinesterase inhibitory activity: Improvement in streptozotocin-induced cognitive deficits in rats

DEMİR ÖZKAY Ü., CAN Ö. D., SAĞLIK B. N., Turan N.

PHARMACOLOGICAL REPORTS, sa.6, ss.1349-1356, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.pharep.2017.06.009
  • Dergi Adı: PHARMACOLOGICAL REPORTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1349-1356
  • Anahtar Kelimeler: Acetylcholinesterase, Molecular docking, Elevated plus maze test, Morris water maze test, Active avoidance test, GAMMA-SECRETASE INHIBITORS, POTENTIAL ANTIDEMENTIA DRUG, N-ARYLSULFONYL PIPERIDINES, ALZHEIMERS-DISEASE, INTRACEREBROVENTRICULAR STREPTOZOTOCIN, OXIDATIVE STRESS, CHOLINESTERASE ACTIVITY, INDUCED NEUROTOXICITY, AMYLOID AGGREGATION, MEMORY IMPAIRMENT
  • Anadolu Üniversitesi Adresli: Evet

Özet

Background: Acetylcholinesterase (AChE) inhibitors are frequently prescribed to mitigate the cognitive decline in Alzheimer's disease. Thus, we investigated the possible efficacy of the AChE inhibitor 2-[(6-Nitro-2-benzothiazolyl) amino]-2-oxoethyl4-[2-(N, N-dimethylamino) ethyl] piperazine-1 carbodithioate (BPCT) in a streptozotocin (STZ)-induced Alzheimer's disease model (SADM). Methods: First, we analyzed the molecular interaction of BPCT with AChE via a docking study. Then, the cognitive effects of BPCT (10 and 20 mg/kg) were evaluated in intracerebroventricular STZ- and vehicle-administered rats with the elevated plus maze (EPM), Morris water maze (MWM), and active avoidance (AA) tests. Locomotor activity was also assessed. Results: Docking analysis indicated significant binding of BPCT to the AChE active site. In behavioral tests, STZ administration impaired cognitive performance in SADM rats versus control rats. Treatment with donepezil or BPCT significantly decreased the prolonged 2nd retention transfer latency and 2nd retention latency time values of the SADM group in the EPM and MWM tests, respectively. Further, prolonged latency times were decreased and reduced frequency of avoidance events were increased in the AA test. Locomotor activity between groups was not different. Conclusion: BPCT appears to function as a central AChE inhibitor, and its improvement of deficits in SADM rats suggests that it has therapeutic potential in Alzheimer's disease. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.