Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F13%3A39896480" target="_blank" >RIV/00216275:25310/13:39896480 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/13:10144118 RIV/62157124:16370/13:43872235

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bmc.2013.01.052" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2013.01.052</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2013.01.052" target="_blank" >10.1016/j.bmc.2013.01.052</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors

Popis výsledku v původním jazyce

A series of novel cholinesterase inhibitors based on 2-substituted 6-?uorobenzo[d]thiazole were synthesised and characterised by IR, 1H, 13C and 19F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested fortheir ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity wasdetermined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound.

Název v anglickém jazyce

Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors

Popis výsledku anglicky

A series of novel cholinesterase inhibitors based on 2-substituted 6-?uorobenzo[d]thiazole were synthesised and characterised by IR, 1H, 13C and 19F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested fortheir ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity wasdetermined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CC - Organická chemie

OECD FORD obor

—

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Bioorganic & Medicinal Chemistry

ISSN

0968-0896

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

1735-1748

Kód UT WoS článku

000316770300014

EID výsledku v databázi Scopus

—