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.

• Klíčová slova
• acetylcholinesterase, arylcarbonyloxyaminopropanols, butyrylcholinesterase, quaternary ammonium salts, tertiary amines,
• MeSH
• acetylcholinesterasa MeSH
• aktivace enzymů účinky léků   MeSH
• benzoáty chemická syntéza   chemie   farmakologie   MeSH
• butyrylcholinesterasa MeSH
• chemické modely MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• kvartérní amoniové sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• molekulární modely * MeSH
• soli chemie   MeSH
• techniky syntetické chemie * MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• benzoáty MeSH
• butyrylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• kvartérní amoniové sloučeniny MeSH
• soli MeSH

Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of (13)C-CP/MAS and (15)N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated.

• Klíčová slova
• CP/MAS NMR spectroscopy, IR spectroscopy, arylcarbonyloxyaminopropanols, phenylpiperazines, principle components analysis, synthesis,
• MeSH
• antihypertenziva chemická syntéza   chemie   MeSH
• benzoáty chemická syntéza   chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• piperazin MeSH
• piperaziny chemie   MeSH
• soli chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antihypertenziva MeSH
• benzoáty MeSH
• piperazin MeSH
• piperaziny MeSH
• soli MeSH

A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.

• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• benzoáty chemická syntéza   farmakologie   MeSH
• karbamáty chemická syntéza   farmakologie   MeSH
• Mycobacterium avium subsp. paratuberculosis účinky léků   MeSH
• rozpřahující látky chemická syntéza   farmakologie   MeSH
• Spinacia oleracea účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• benzoáty MeSH
• karbamáty MeSH
• rozpřahující látky MeSH