Synthesis, analysis, cholinesterase-inhibiting activity and molecular modelling studies of 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxy-carbonyl)amino]benzoates and their quaternary ammonium salts

0483037 - ÚVGZ 2019 RIV CH eng J - Journal Article
Padrtova, T. - Marvanová, P. - Odehnalová, K. - Kubínová, R. - Parravicini, V. - Garro, A. - Enriz, R. D. - Humpa, O. - Oravec, Michal - Mokrý, P.
Synthesis, analysis, cholinesterase-inhibiting activity and molecular modelling studies of 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxy-carbonyl)amino]benzoates and their quaternary ammonium salts.
Molecules. Roč. 22, č. 12 (2017), č. článku 2048. E-ISSN 1420-3049
R&D Projects: GA MŠMT(CZ) LM2015061; GA MŠMT(CZ) LO1415; GA MŠMT(CZ) EF16_013/0001609
Research Infrastructure: CzeCOS II - 90061
Institutional support: RVO:86652079
Keywords : Acetylcholinesterase * Arylcarbonyloxyaminopropanols * Butyrylcholinesterase * Quaternary ammonium salts * Tertiary amines
OECD category: Biochemistry and molecular biology
Impact factor: 3.098, year: 2017

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 (pK a ) 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.
Permanent Link: http://hdl.handle.net/11104/0278463