文章基本信息

标题：Simplified Heterocyclic Analogues of Fluoxetine Inhibit Inducible Nitric Oxide Production in Lipopolysaccharide-Induced BV2 Cells
本地全文：下载
作者：Ju-Young Park ; Seung-Woo Kim ; Ja-Kyeong Lee 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2011
卷号：34
期号：4
页码：538-544
DOI：10.1248/bpb.34.538
出版社：The Pharmaceutical Society of Japan
摘要：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 μ M 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.
关键词：fluoxetine analogue;microglia;BV2 cell;nitric oxide;inducible nitric oxide synthase