Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts

MOKRY, PETR; ENRIZ, RICARDO; KUBINOVA, RENATA; PADRTOVA, TEREZA; HUMPA, OTAKAR; ORAVEC, MICHAL; PARRAVICINI, OSCAR; GARRO, ADRIANA; MARVANOVA, PAVLINA; ODEHNALOVA, KLARA; MOKRY, PETR; ENRIZ, RICARDO; KUBINOVA, RENATA; PADRTOVA, TEREZA; HUMPA, OTAKAR; PARRAVICINI, OSCAR; MARVANOVA, PAVLINA; ORAVEC, MICHAL; GARRO, ADRIANA; ODEHNALOVA, KLARA

MOLECULES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2017 vol. 22

1420-3049

Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoatesand their quaternary ammonium salts were synthesized. The final step of synthesis of quaternaryammonium salts was carried out by microwave-assisted synthesis. Software-calculated data providedthe background needed to compare fifteen new resulting compounds by their physicochemicalproperties. The acid dissociation constant (pK a ) and lipophilicity index (log P) of tertiary amineswere determined; while quaternary ammonium salts were characterized by software-calculatedlipophilicity index and surface tension. Biological evaluation aimed at testing acetylcholinesteraseand butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible mechanism ofaction of these compounds was determined by molecular modelling study using combined techniquesof docking; molecular dynamics simulations and quantum mechanics calculations.