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

Background: 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. 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 (icv) 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 (1,5,and 10 mg/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. 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 icv stz-injected rats. potencies of these test compounds were comparable to the activity of dnp. copyright © 2012 by institute of pharmacology polish academy of sciences.