Synthesis and evaluation of new 2-oxo-1,2-dihydroquinoline-3-carboxamides as potent inhibitors against acetylcholinesterase enzyme.

Alzheimer's disease (AD), a worldwide mental disorder manifested with dementia symptoms, was used to be treated with tacrine. The latter use was terminated recently due to its hepatotoxicity. Thus, synthesis of tacrine analogues free of hepatotoxicity was attempted, a group of new 2-oxo-1,2-dihydroquinoline-3-carboxamides have been synthesized and properly characterized. Their biological evaluation in inhibiting acetylcholinesterase enzyme (AChE), was evaluated by the in-house gas chromatography method. The synthesized carboxamides showed a strong potency in inhibiting AChE. Nine compounds from the group had activities higher than or close to donepezil (the positive control, IC50 ca 10 nM). For example, compound 7 depicted IC50 of 7 nM and was subsequently evaluated by the in vivo zebra fish model. Interestingly compound 7 showed better recovery from scopolamine-induced dementia than that of donepezil. Further ex vivo and in vivo models have been established recently in the lab to evaluate the safety of these compounds. [ABSTRACT FROM AUTHOR]