title: Simplified heterocyclic analogues of fluoxetine inhibit inducible nitric oxide production in lipopolysaccharide-induced BV2 cells.
abstract: A series of fluoxetine, where the N-methylamino group was replaced and then simplified, were synthesized and their inhibitory effect was tested for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells. Although the synthesized compounds generally revealed weaker activity or greater cytotoxicity than fluoxetine, compound 10a, in which the N-methylamino group in fluoxetine was replaced by morpholine, and the trifluoromethylphenyl ring was substituted with simple oxo group, suppressed NO production dose-dependently at 10, 20 and 40 µM concentrations with less cytotoxicity than fluoxetine, and inhibited iNOS mRNA and protein expression at the same concentrations in LPS-induced BV2 cells. The results suggested that the trifluoromethylphenyl ring moiety in fluoxetine is not necessary for the suppression of NO production and that 10a has the potential as a potent inhibitor of NO production.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Kim
authors.forename: Ja-Kyeong
authors.initials: JK
authors.lastname: Lee
authors.forename: Weon Bin
authors.initials: WB
authors.lastname: Im
authors.forename: Byung Kwan
authors.initials: BK
authors.lastname: Jin
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Yoon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006571:Heterocyclic Compounds; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D005473:Fluoxetine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II