Login for students

Login for employees

Publication detail

Synthesis, structural characterization, docking, lipophilicity and cytotoxicity of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl carbamates, novel acetylcholinesterase and butyrylcholinesterase pseudo-irreversible inhibitors
Authors: Pejchal Vladimír | Štěpánková Šárka | Pejchalová Marcela | Královec Karel | Havelek Radim | Růžičková Zdeňka | Ajani Haresh | Lo Rabindranath | Lepsik Martin
Year: 2016
Type of publication: článek v odborném periodiku
Name of source: Bioorganic & Medicinal Chemistry
Page from-to: 1560-1572
Titles:
Language Name Abstract Keywords
cze Syntéza, strukturní charakterizace, docking, lipofilita a cytotoxicita 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl karbamátů, nových acetylcholinesteráz a butyrylcholinesteráz pseudo-ireverzibilních inhibitorů Publikace se věnuje syntéze, strukturní charakterizaci, docking, lipofilitě a cytotoxicitě 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl karbamátů, nových acetylcholinesteráz a butyrylcholinesteráz pseudo-ireverzibilních inhibitorů. Halogenované benzothiazoly; karbamáty; acetylcholinesteráza; inhibice butyrylcholinesterázy; pseudo-irreversibilní mechanismus; kovalentní docking
eng Synthesis, structural characterization, docking, lipophilicity and cytotoxicity of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl carbamates, novel acetylcholinesterase and butyrylcholinesterase pseudo-irreversible inhibitors In the current study, sixteen novel derivatives of (R)-1-(6-fluorobenzo[d]thiazol-2-yl) ethanamine were synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. Chemical structures together with purity of the synthesized compounds were substantiated by IR, H-1, C-13, F-19 NMR, high resolution mass spectrometry and elemental analysis. The optical activities were confirmed by optical rotation measurements. The synthesized compounds were evaluated for their AChE and BChE inhibitory activities. In addition, the cytotoxicity of the most active compounds was investigated against human cell lines employing XTT tetrazolium salt reduction assay and xCELLigence system allowing a label-free assessment of the cells proliferation. Our results demonstrated that the inhibitory mechanism was confirmed to be pseudo-irreversible, in line with previous studies on carbamates. Compounds indicated as 3b, 3d, 3l and 3n showed the best AChE inhibitory activity of all the evaluated compounds and were up to tenfold more potent than standard drug rivastigmine. The binding mode was determined using state-of-the-art covalent docking and scoring methodology. The obtained data clearly demonstrated that 3b, 3d, 3l and 3n benzothiazole carbamates possess high inhibitory activity against AChE and BChE and concurrently negligible cytotoxicity. In conclusion, our results indicate, that these derivatives could be promising in an effective therapeutic intervention for Alzheimer's disease. Halogenated benzothiazole; Carbamates; Acetylcholinesterase; Butyrylcholinesterase inhibition; Pseudo-irreversible mechanism; Covalent docking

Departments

Other Parts

Map

en.mapy.cz

Services

Popular Links

© 2023 University of Pardubice, Studentská 95, 532 10 Pardubice 2
Phone: +420 466 036 111, 466 036 112, 466 036 113
Webmaster, RSS
Data box ID: f5vj9hu
Accessibility Statement
CC BY-NC-ND 4.0Creative CommonsAttributionNonCommercialNoDerivatives