Synthesis and Biological Activity of New 2,3-dihydro-1H-cyclopenta[b]- quinoline Derivatives as Acetylcholinesterase Inhibitors

Pawel      Szymanski; Magdalena      Markowicz; Marek      Bajda; Barbara      Malawska; Elzbieta      Mikiciuk-Olasik

Abstract

In this study we present synthesis and biological evaluation of derivatives of 4-fluorobenzoic acid and 2,3- dihydro-1H-cyclopenta[b]quinoline towards inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Synthesis of acquired molecules involved the reaction of condensation between the activated 4-fluorobenzoic acid and amino derivatives of 2,3-dihydro-1H-cyclopenta[b]quinoline. Biological testing towards the inhibition of cholinesterases was conducted according to the Ellman’s spectrophotometric method. Compounds 4b and 4e were found to be less active in comparison with tacrine. However, compounds 4d, 4g and 4h showed similar activity to tacrine. Compounds 4a, 4c and 4f were more active towards inhibition of AChE than tacrine. Every synthesized compound displayed higher selectivity towards AChE and lower selectivity towards BChE in comparison with tacrine apart from compound 4b. Compound 4b was characterized by similar selectivity towards AChE and higher selectivity towards BChE than tacrine.

Keywords: Acetylcholinesterase inhibitors, Alzheimer’s disease, Cyclopenta[b]quinoline, Ellman method, Fluorobenzoic acid, molecular docking, 2, 3-dihydro-1H-cyclopenta[b]quinoline, butyrylcholinesterase (BChE), acetylcholinesterase (AChE) , Ellman’s spectrophotometric method, neurodegeneration, Pathologic lesions, neuronal loss, parietal and occipital cortices, donepezil