Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts
Tereza Padrtova,
Pavlina Marvanova,
Klara Odehnalova,
Renata Kubinova,
Oscar Parravicini,
Adriana Garro,
Ricardo D. Enriz,
Otakar Humpa,
Michal Oravec,
Petr Mokry
Affiliations
Tereza Padrtova
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic
Pavlina Marvanova
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic
Klara Odehnalova
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic
Renata Kubinova
Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic
Oscar Parravicini
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis-IMIBIO-SL-CONICET, Chacabuco 915, San Luis 5700, Argentina
Adriana Garro
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis-IMIBIO-SL-CONICET, Chacabuco 915, San Luis 5700, Argentina
Ricardo D. Enriz
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis-IMIBIO-SL-CONICET, Chacabuco 915, San Luis 5700, Argentina
Otakar Humpa
CEITEC–Central European Institute of Technology, Masaryk University, Kamenice 753/5, 62500 Brno, Czech Republic
Michal Oravec
Global Change Research Institute CAS, Belidla 986/4a, 60300 Brno, Czech Republic
Petr Mokry
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic
Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The acid dissociation constant (pKa) and lipophilicity index (log P) of tertiary amines were determined; while quaternary ammonium salts were characterized by software-calculated lipophilicity index and surface tension. Biological evaluation aimed at testing acetylcholinesterase and butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible mechanism of action of these compounds was determined by molecular modelling study using combined techniques of docking; molecular dynamics simulations and quantum mechanics calculations.
