title: AETIQ: a novel synthetic compound with anti-inflammatory properties in activated microglia.
abstract: Neuroinflammation is believed to be involved in the pathogenesis of neurodegenerative diseases. Our novel synthetic compound 2-acetyl-1-ethyl-7-hydroxy-6-methoxy-1, 2, 3, 4-tetrahydroisoquinoline (AETIQ) was tested for its anti-inflammatory properties in activated microglial BV-2 cells. AETIQ attenuated nitric oxide (NO) and reactive oxygen species generation. It also downregulated the production of the proinflammatory enzymes inducible NO synthase, cyclooxygenase-2, and matrix metalloproteinase-3 at both mRNA and protein levels. Furthermore, AETIQ suppressed generation of the proinflammatory cytokines IL-1β and TNF-α as determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and ELISA assays. AETIQ attenuated NFκB signaling by downregulating NFκB nuclear translocation. The compound was stable against the liver enzymes in the microsomal and S9 fractions, indicative of good bioavailability. These results suggested that AETIQ might be utilized towards development of a therapy for neuroinflammation-related diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 138-736, South Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Son
authors.forename: Nari
authors.initials: N
authors.lastname: Shin
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Shin
authors.forename: Dae Yoon
authors.initials: DY
authors.lastname: Chi
authors.forename: Jai Woong
authors.initials: JW
authors.lastname: Seo
authors.forename: Cheol Soon
authors.initials: CS
authors.lastname: Lee
authors.forename: Onyou
authors.initials: O
authors.lastname: Hwang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000276:immunology; D015213:Neuroimmunomodulation / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C000598525:2-acetyl-1-ethyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline; D000893:Anti-Inflammatory Agents; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D044005:Tetrahydroisoquinolines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse