Eleven piperazine-containing 1,3-diphenylprop-2-en-1-one derivatives (PC1-PC11) were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with a view toward developing new treatments for neurological disorders. Compounds PC10 and PC11 remarkably inhibited MAO-B with IC50 values of 0.65 and 0.71 μM, respectively. Ten of the eleven compounds weakly inhibited AChE and BChE with > 50% of residual activities at 10 μM, although PC4 inhibited AChE by 56.6% (IC50 = 8.77 μM). Compound PC3 effectively inhibited BACE-1 (IC50 = 6.72 μM), and PC10 and PC11 moderately inhibited BACE-1 (IC50 =14.9 and 15.3 μM, respectively). Reversibility and kinetic studies showed that PC10 and PC11 were reversible and competitive inhibitors of MAO-B with Ki values of 0.63 ± 0.13 and 0.53 ± 0.068 μM, respectively. ADME predictions for lead compounds revealed that PC10 and PC11 have central nervous system (CNS) drug-likeness. Molecular docking simulations showed that fluorine atom and trifluoromethyl group on PC10 and PC11, respectively, interacted with the substrate cavity of the MAO-B active site. Our results suggested that PC10 and PC11 can be considered potential candidates for the treatment of neurological disorders such as Alzheimer's disease and Parkinson's disease.
Keywords: Acetylcholinesterase; Chalcone; Monoamine oxidase; Piperazine.
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.