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

Result code in 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>

Alternative codes found

RIV/61989592:15310/18:73591905

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10609 - Biochemical research methods

Project

<a href="/en/project/LO1204" target="_blank" >LO1204: Sustainable development of research in the Centre of the Region Haná</a><br>

Continuities

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

Publication year

2018

Confidentiality

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

Name of the periodical

Archiv der Pharmazie

ISSN

0365-6233

e-ISSN

—

Volume of the periodical

351

Issue of the periodical within the volume

3-4

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

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UT code for WoS article

000428990000006

EID of the result in the Scopus database

2-s2.0-85041582657