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

• Published in: Pharmacological reports 2012, Vol.64 (4), p.834-847
• Main Authors: Ozkay, Umide Demir, Can, Ozgür Devrim, Ozkay, Yusuf, Oztürk, Yusuf
• Format: Article
• Language: English
• Subjects: acetylcholinesterase; Acetylcholinesterase - metabolism; active avoidance test; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Avoidance Learning - drug effects; benzothiazole/piperazine; Benzothiazoles - pharmacology; Cognition Disorders - chemically induced; Cognition Disorders - drug therapy; Cognition Disorders - metabolism; Disease Models, Animal; donepezil; Drug Safety and Pharmacovigilance; elevated plus maze test; Maze Learning - drug effects; Memory - drug effects; Morris water maze test; Motor Activity - drug effects; Pharmacotherapy; Pharmacy; Piperazines - pharmacology; Rats; Rats, Wistar; Streptozocin; streptozotocin
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(12)70878-2

In this study, benzothiazole-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. 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 (icv) injection of STZ (3mg/kg), bilaterally. The elevated plus maze, Morris water maze, and active avoidance tests were used to examine the effects of test compounds (1,5, and 10mg/kg) on learning and memory parameters of icv STZ-injected rats. Effects of the test compounds on spontaneous locomotor activities of rats were examined with the activity cage test. The compounds B2–B5 and DNP exhibited significant selective inhibitory potencies against acetylcholinesterase. Compounds B2 and B3 at 10mg/kg doses and compounds B4 and B5 at 5 and 10mg/kg doses, as well as the reference drug DNP (1 and 3mg/kg), significantly improved the learning and memory parameters of animals in all cognition tests. None of the test compounds changed spontaneous locomotor activities. Results of the present study revealed that compounds B2-B5 repaired the parameters related to the learning and memory deficits of icv STZ-injected rats. Potencies of these test compounds were comparable to the activity of DNP.