Design and synthesis of thiophenone and furanthione butenolide bioisosteres with inhibitory activity towards acetylcholinesterase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00561033" target="_blank" >RIV/61388963:_____/22:00561033 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.molstruc.2022.133831" target="_blank" >https://doi.org/10.1016/j.molstruc.2022.133831</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molstruc.2022.133831" target="_blank" >10.1016/j.molstruc.2022.133831</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Design and synthesis of thiophenone and furanthione butenolide bioisosteres with inhibitory activity towards acetylcholinesterase

Popis výsledku v původním jazyce

A library of butenolide bioisosteres with sulfur incorporated in the molecule was synthetized and used for the structure-activity relationship studies associated with their inhibitory activity towards the AChE enzyme. Modifications through bioisosteric exchange of oxygen for sulfur either in position one of the butenolide ring (thiophenones) or on C2 (furanthiones) and further modification of the backbone via nucleophilic alkylation resulted in differential binding with the AChE enzyme. In general, the furanthiones were more efficient at binding AChE while some of the thiophenones were predicted to be toxic. Compound 11a, a C5 disubstituted furan-2(5H)-thione containing both the methyl and the isopropyl groups at C5 displayed the most encouraging inhibitory activity towards AChE. Molecular dynamics simulations in terms of the RMSD and RMSF trajectories and intermolecular bond analysis revealed considerable stability of the complex. Reactivity of 11a was further validated by quantum chemical calculations using DFT.

Název v anglickém jazyce

Design and synthesis of thiophenone and furanthione butenolide bioisosteres with inhibitory activity towards acetylcholinesterase

Popis výsledku anglicky

A library of butenolide bioisosteres with sulfur incorporated in the molecule was synthetized and used for the structure-activity relationship studies associated with their inhibitory activity towards the AChE enzyme. Modifications through bioisosteric exchange of oxygen for sulfur either in position one of the butenolide ring (thiophenones) or on C2 (furanthiones) and further modification of the backbone via nucleophilic alkylation resulted in differential binding with the AChE enzyme. In general, the furanthiones were more efficient at binding AChE while some of the thiophenones were predicted to be toxic. Compound 11a, a C5 disubstituted furan-2(5H)-thione containing both the methyl and the isopropyl groups at C5 displayed the most encouraging inhibitory activity towards AChE. Molecular dynamics simulations in terms of the RMSD and RMSF trajectories and intermolecular bond analysis revealed considerable stability of the complex. Reactivity of 11a was further validated by quantum chemical calculations using DFT.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA20-11571S" target="_blank" >GA20-11571S: Butenolidy s neuroprotektivními účinky vyskytující se v kouři z rostlinného materiálu a jejich syntetické deriváty</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Journal of Molecular Structure

ISSN

0022-2860

e-ISSN

1872-8014

Svazek periodika

1269

Číslo periodika v rámci svazku

December

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

133831

Kód UT WoS článku

000877094300006

EID výsledku v databázi Scopus

2-s2.0-85136657124