title: Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB.
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.
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: PullaReddy
authors.initials: P
authors.lastname: Boggu
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Eeda
authors.initials: E
authors.lastname: Venkateswararao
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Manoj
authors.initials: M
authors.lastname: Manickam
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Dajin
authors.initials: D
authors.lastname: Kwak
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Jung
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D016328:NF-kappa B; C004453:bendazole
keywords: 2-Benzylbenzimidazole; Inflammation; NF-κB inhibition