Novel c-Jun N-Terminal Kinase (JNK) Inhibitors with an 11H-Indeno[1,2-b]quinoxalin-11-one Scaffold

Novel c-Jun N-Terminal Kinase (JNK) Inhibitors with an 11H-Indeno[1,2-b]quinoxalin-11-one Scaffold

Bibliographic Details
Parent link:Molecules
Vol. 26, iss. 18.— 2021.— [5688, 18 p.]
Corporate Author: Национальный исследовательский Томский политехнический университет Инженерная школа новых производственных технологий Научно-образовательный центр Н. М. Кижнера
Other Authors: Lyakhov S. A. Sergey, Shchepyotkin I. A. Igor Aleksandrovich, Karpenko A. S. Alexander, Duma N. I. Nanna, Gaidarzhy N. M. Nadiya, Kirpotina L. N. Liliya Nikolaevna, Kovrizhina A. R. Anastasia Ruslanovna, Khlebnikov A. I. Andrey Ivanovich, Bagryanskaya I. Yu. Irina Yurjevna, Quinn M. T. Mark
Summary:Title screen
c-Jun N-terminal kinase (JNK) plays a central role in stress signaling pathways implicated in important pathological processes, including rheumatoid arthritis and ischemia-reperfusion injury. Therefore, inhibition of JNK is of interest for molecular targeted therapy to treat various diseases. We synthesized 13 derivatives of our reported JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime and evaluated their binding to the three JNK isoforms and their biological effects. Eight compounds exhibited submicromolar binding affinity for at least one JNK isoform. Most of these compounds also inhibited lipopolysaccharide (LPS)-induced nuclear factor-kB/activating protein 1 (NF-kB/AP-1) activation and interleukin-6 (IL-6) production in human monocytic THP1-Blue cells and human MonoMac-6 cells, respectively. Selected compounds (4f and 4m) also inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. We conclude that indenoquinoxaline-based oximes can serve as specific small-molecule modulators for mechanistic studies of JNKs, as well as potential leads for the development of anti-inflammatory drugs.
Language:English
Published: 2021
Subjects:
труды учёных ТПУ
электронный ресурс
c-Jun N-terminal kinase
kinase inhibitor
11H-indeno[1,2-b]quinoxalin-11-one
oxime
interleukin-6
nuclear factor-kB
ингибиторы
киназы
терапия
противовоспалительные препараты
Online Access:https://doi.org/10.3390/molecules26185688
Format: Electronic Book Chapter
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=666255

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