Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocin-induced cognitive deficits

Demir Özkay Ü., Can Ö. D., Özkay Y., Öztürk Y.

PHARMACOLOGICAL REPORTS, sa.4, ss.834-847, 2012 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1016/s1734-1140(12)70878-2
  • Dergi Adı: PHARMACOLOGICAL REPORTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.834-847
  • Anahtar Kelimeler: Alzheimer's disease, streptozotocin, donepezil, acetylcholinesterase, elevated plus maze test, Morris water maze test, active avoidance test, benzothiazole/piperazine, POTENTIAL ANTIDEMENTIA DRUG, GAMMA-SECRETASE INHIBITORS, N-ARYLSULFONYL PIPERIDINES, ALZHEIMERS-DISEASE, ACETYLCHOLINESTERASE INHIBITOR, INDUCED NEUROTOXICITY, HIPPOCAMPAL SLICES, MEMORY IMPAIRMENT, FRONTAL-CORTEX, RATS
  • Anadolu Üniversitesi Adresli: Evet

Özet

Background: In this study, benzothiazolc-piperazine compounds were synthesized by condensing the functional groups of donepezil (DNP), FK-960, and sabeluzole, which are known to have therapeutic potential against Alzheimer's disease, with the aim of obtaining new and potent anti-Alzheimer agents. Methods: Initially, acetylcholinesterase/butyrylcholinesterase enzyme inhibition activities of the synthesized test compounds were investigated by Ellman's method. Effects of the compounds on a streptozotocin (STZ) model of Alzheimer's disease (SMAD) were investigated in rats. SMAD was established by intracerebroventricular (icy) injection of STZ (3 mg/kg), bilaterally. The elevated plus maze, Morris water maze, and active avoidance tests were used to examine the effects of test compounds (I, 5, and 10 mg/kg) on learning and memory parameters of icy STZ-injected rats. Effects of the test compounds on spontaneous locomotor activities of rats were examined with the activity cage test. Results: The compounds B2-B5 and DNP exhibited significant selective inhibitory potencies against acetylcholinesterase. Compounds B2 and B3 at 10 mg/kg doses and compounds B4 and B5 at 5 and 10 mg/kg doses, as well as the reference drug DNP (1 and 3 mg/kg), significantly improved the learning and memory parameters of animals in all cognition tests. None of the test compounds changed spontaneous locomotor activities. Conclusion: Results of the present study revealed that compounds B2-B5 repaired the parameters related to the learning and memory deficits of icy STZ-injected rats. Potencies of these test compounds were comparable to the activity of DNP.