title: 4-Isopropyl-2,6-bis(1-phenylethyl)aniline 1, an Analogue of KTH-13 Isolated from Cordyceps bassiana, Inhibits the NF-κB-Mediated Inflammatory Response.
abstract: The Cordyceps species has been a good source of compounds with anticancer and anti-inflammatory activities. Recently, we reported a novel compound (4-isopropyl-2,6-bis(1-phenylethyl)phenol, KTH-13) with anticancer activity isolated from Cordyceps bassiana and created several derivatives to increase its pharmacological activity. In this study, we tested one of the KTH-013 derivatives, 4-isopropyl-2,6-bis(1-phenylethyl)aniline 1 (KTH-13-AD1), with regard to anti-inflammatory activity under macrophage-mediated inflammatory conditions. KTH-13-AD1 clearly suppressed the production of nitric oxide (NO) and reactive oxygen species (ROS) in lipopolysaccharide (LPS) and sodium nitroprusside- (SNP-) treated macrophage-like cells (RAW264.7 cells). Similarly, this compound also reduced mRNA expression of inducible NO synthase (iNOS) and tumor necrosis factor-α (TNF-α), as analyzed by RT-PCR and real-time PCR. Interestingly, KTH-13-AD1 strongly diminished NF-κB-mediated luciferase activities and nuclear translocation of NF-κB family proteins. In accordance, KTH-13-AD1 suppressed the upstream signaling pathway of NF-κB activation, including IκBα, IKKα/β, AKT, p85/PI3K, and Src in a time- and dose-dependent manner. The autophosphorylation of Src and NF-κB observed during the overexpression of Src was also suppressed by KTH-13-AD1. These results strongly suggest that KTH-13-AD1 has strong anti-inflammatory features mediated by suppression of the Src/NF-κB regulatory loop.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Department of Pediatrics, Institute of Child and Maternal Health (ICMH), Matuail, Dhaka 1362, Bangladesh.
authors.forename: Zubair Ahmed
authors.initials: ZA
authors.lastname: Ratan
authors.affiliation: Department of Chemistry, Kwangwoon University, Seoul 139-701, Republic of Korea.
authors.forename: Gihyeon
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Kwangwoon University, Seoul 139-701, Republic of Korea.
authors.forename: Yunmi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: School of Systems Biological Science, Soongsil University, Seoul 156-743, Republic of Korea.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Veterinary Medicine, Chonbuk National University, 79 Gobong-ro, Iksan 54596, Republic of Korea.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D032661:Cordyceps / Q000737:chemistry*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000502:physiology
chemical_list: C000611052:4-isopropyl-2,6-bis(1-phenylethyl)aniline; D000814:Aniline Compounds; D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D009569:Nitric Oxide
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