Arylaminopropanone Derivatives as Potential Cholinesterase Inhibitors: Synthesis, Docking Study and Biological Evaluation

HUDCOVÁ, ANNA; KROUTIL, ALE?; KUBÍNOVÁ, RENATA; GARRO, ADRIANA D.; GUTIERREZ, LUCAS J.; ENRIZ, DANIEL; ORAVEC, MICHAL; CSÖLLEI, JOZEF

MOLECULES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2020 vol. 25

1420-3049

Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1-16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1-3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.