Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB

Bioorganic & Medicinal Chemistry
2016.0

Abstract

For finding the novel inhibitor of nuclear factor κB activity, a series of benzimidazole derivatives were rationally designed, synthesized and systematically studied for their in vitro activities against LPS induced NF-κB inhibition in RAW 264.7 cells using the SEAP assay based on the flexible chalcone JSH ((E)-1-(2-hydroxy-6-(isopentyloxy)phenyl)-3-(4-hydroxy phenyl)prop-2-en-1-one) which was previously reported. Although most of the benzimidazole derivatives showed strong inhibitory activity in low micromolar potency, 2-(4-methoxybenzyl)-1H-benzo[d]imidazole (3m; IC50=1.7 μM) and 2-(2-methoxybenzyl)-1H-benzo[d]imidazole (3n; IC50=2.4 μM) showed the best inhibition. The structure activity relationship revealed that 2-benzylbenzimidazole scaffold with hydrogen bonding acceptor on phenyl ring appears as a pharmacophore.

DOI： 10.1016/j.bmc.2016.03.012

Knowledge Graph

Similar Paper

Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB
Bioorganic & Medicinal Chemistry 2016.0
Design, synthesis, and biological evaluation of benzofuran- and 2,3-dihydrobenzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives as anticancer agents and inhibitors of NF-κB
Bioorganic & Medicinal Chemistry Letters 2015.0
Study on anti-proliferative effect of benzoxathiole derivatives through inactivation of NF-κB in human cancer cells
Bioorganic & Medicinal Chemistry Letters 2012.0
Design and synthesis of 3,4-dihydro-2H-benzo[h]chromene derivatives as potential NF-κB inhibitors
Bioorganic & Medicinal Chemistry Letters 2014.0
Discovery of novel NF-кB inhibitor based on scaffold hopping: 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine
European Journal of Medicinal Chemistry 2020.0
Discovery of novel antitumor dibenzocyclooctatetraene derivatives and related biphenyls as potent inhibitors of NF-κB signaling pathway
Bioorganic & Medicinal Chemistry 2014.0
Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1 H -benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects
Bioorganic & Medicinal Chemistry 2013.0
Benzobis(imidazole) derivatives as STAT3 signal inhibitors with antitumor activity
Bioorganic & Medicinal Chemistry 2022.0
Design, synthesis and evaluation of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase
Bioorganic & Medicinal Chemistry 2011.0
N-phenylsulfonyl-3,5-bis(arylidene)-4-piperidone derivatives as activation NF-κB inhibitors in hepatic carcinoma cell lines
European Journal of Medicinal Chemistry 2018.0