2. Academic Validation
  3. Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB

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

  • Bioorg Med Chem. 2016 Apr 15;24(8):1872-8. doi: 10.1016/j.bmc.2016.03.012.
PullaReddy Boggu 1,  Eeda Venkateswararao 1,  Manoj Manickam 1,  Dajin Kwak 2,  Youngsoo Kim 2,  Sang-Hun Jung 3
Affiliations

Affiliations

  • 1 College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
  • 2 College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
  • 3 College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: jungshh@cnu.ac.kr.
PMID: 26976506 DOI: 10.1016/j.bmc.2016.03.012
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.

Keywords

2-Benzylbenzimidazole; Inflammation; NF-κB inhibition.

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