Design, synthesis, and biological evaluation of novel 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives as cytotoxic agents and COX-2/LOX inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F18%3A00488993" target="_blank" >RIV/61389030:_____/18:00488993 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/18:73591905

Výsledek na webu

<a href="http://dx.doi.org/10.1002/ardp.201700311" target="_blank" >http://dx.doi.org/10.1002/ardp.201700311</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ardp.201700311" target="_blank" >10.1002/ardp.201700311</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Design, synthesis, and biological evaluation of novel 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives as cytotoxic agents and COX-2/LOX inhibitors

Popis výsledku v původním jazyce

A new series of 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives 4a–l was synthesized. Their structures were confirmed by different spectroscopic techniques (IR, 1 H NMR, DEPT-Q NMR, and mass spectroscopy) and elemental analyses. Their cytotoxic activities in vitro were evaluated against breast, ovarian, and liver cancer cell lines and also normal human skin fibroblasts. Cyclooxygenase (COX)-1, COX-2 and lipoxygenase (LOX) inhibitory activities were measured. The synthesized compounds showed selectivity toward COX-2 rather than COX-1, and the IC 50 values (0.25–1.7 µM) were lower than that of indomethacin (IC 50 = 9.47 µM) and somewhat higher than that of celecoxib (IC 50 = 0.071 µM). The selectivity index for COX-2 of the oxazole derivative 4e (SI = 3.67) was nearly equal to that of celecoxib (SI = 3.66). For the LOX inhibitory activity, the new compounds showed IC 50 values of 0.02–74.03 µM, while the IC 50 of the reference zileuton was 0.83 µM. The most active compound 4c (4-chlorobenzoxazole derivative) was found to have dual COX-2/LOX activity. All the synthesized compounds were docked inside the active site of the COX-2 and LOX enzymes. They linked to COX-2 through the N atom of the azole scaffold, while CO of the oxazolone moiety was responsible for the binding to amino acids inside the LOX active site.

Název v anglickém jazyce

Design, synthesis, and biological evaluation of novel 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives as cytotoxic agents and COX-2/LOX inhibitors

Popis výsledku anglicky

A new series of 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives 4a–l was synthesized. Their structures were confirmed by different spectroscopic techniques (IR, 1 H NMR, DEPT-Q NMR, and mass spectroscopy) and elemental analyses. Their cytotoxic activities in vitro were evaluated against breast, ovarian, and liver cancer cell lines and also normal human skin fibroblasts. Cyclooxygenase (COX)-1, COX-2 and lipoxygenase (LOX) inhibitory activities were measured. The synthesized compounds showed selectivity toward COX-2 rather than COX-1, and the IC 50 values (0.25–1.7 µM) were lower than that of indomethacin (IC 50 = 9.47 µM) and somewhat higher than that of celecoxib (IC 50 = 0.071 µM). The selectivity index for COX-2 of the oxazole derivative 4e (SI = 3.67) was nearly equal to that of celecoxib (SI = 3.66). For the LOX inhibitory activity, the new compounds showed IC 50 values of 0.02–74.03 µM, while the IC 50 of the reference zileuton was 0.83 µM. The most active compound 4c (4-chlorobenzoxazole derivative) was found to have dual COX-2/LOX activity. All the synthesized compounds were docked inside the active site of the COX-2 and LOX enzymes. They linked to COX-2 through the N atom of the azole scaffold, while CO of the oxazolone moiety was responsible for the binding to amino acids inside the LOX active site.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10609 - Biochemical research methods

Projekt

<a href="/cs/project/LO1204" target="_blank" >LO1204: Udržitelný rozvoj výzkumu v Centru regionu Haná</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Archiv der Pharmazie

ISSN

0365-6233

e-ISSN

—

Svazek periodika

351

Číslo periodika v rámci svazku

3-4

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

—

Kód UT WoS článku

000428990000006

EID výsledku v databázi Scopus

2-s2.0-85041582657