Simplified Heterocyclic Analogues of Fluoxetine Inhibit Inducible Nitric Oxide Production in Lipopolysaccharide-Induced BV2 Cells
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 compoun...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2011/04/01, Vol.34(4), pp.538-544 |
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| container_title | Biological & pharmaceutical bulletin |
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| creator | Park, Ju-Young Kim, Seung-Woo Lee, Ja-Kyeong Im, Weon Bin Jin, Byung Kwan Yoon, Sung-Hwa |
| description | 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. |
| doi_str_mv | 10.1248/bpb.34.538 |
| format | Article |
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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.</description><identifier>ISSN: 0918-6158</identifier><identifier>ISSN: 1347-5215</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.34.538</identifier><identifier>PMID: 21467642</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Anti-Inflammatory Agents - chemical synthesis ; Anti-Inflammatory Agents - pharmacology ; BV2 cell ; Cell Line ; Dose-Response Relationship, Drug ; Fluoxetine - analogs & derivatives ; Fluoxetine - pharmacology ; fluoxetine analogue ; Heterocyclic Compounds - chemical synthesis ; Heterocyclic Compounds - pharmacology ; inducible nitric oxide synthase ; Lipopolysaccharides ; Mice ; microglia ; nitric oxide ; Nitric Oxide - biosynthesis ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; RNA, Messenger - metabolism</subject><ispartof>Biological and Pharmaceutical Bulletin, 2011/04/01, Vol.34(4), pp.538-544</ispartof><rights>2011 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-7123d1b4d9753aede3627728801d4ea9e81204984a028e1a4794cc38d35ce4493</citedby><cites>FETCH-LOGICAL-c529t-7123d1b4d9753aede3627728801d4ea9e81204984a028e1a4794cc38d35ce4493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21467642$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Ju-Young</creatorcontrib><creatorcontrib>Kim, Seung-Woo</creatorcontrib><creatorcontrib>Lee, Ja-Kyeong</creatorcontrib><creatorcontrib>Im, Weon Bin</creatorcontrib><creatorcontrib>Jin, Byung Kwan</creatorcontrib><creatorcontrib>Yoon, Sung-Hwa</creatorcontrib><title>Simplified Heterocyclic Analogues of Fluoxetine Inhibit Inducible Nitric Oxide Production in Lipopolysaccharide-Induced BV2 Cells</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>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.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - chemical synthesis</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>BV2 cell</subject><subject>Cell Line</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fluoxetine - analogs & derivatives</subject><subject>Fluoxetine - pharmacology</subject><subject>fluoxetine analogue</subject><subject>Heterocyclic Compounds - chemical synthesis</subject><subject>Heterocyclic Compounds - pharmacology</subject><subject>inducible nitric oxide synthase</subject><subject>Lipopolysaccharides</subject><subject>Mice</subject><subject>microglia</subject><subject>nitric oxide</subject><subject>Nitric Oxide - biosynthesis</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>RNA, Messenger - metabolism</subject><issn>0918-6158</issn><issn>1347-5215</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtrGzEURkVpady0m_6AIugipTCunjPSqiSmaQImKfSxHTSa60RGHk0lDcTL_PPIdeJFF9nognTudyUdhN5TMqdMqC_d2M25mEuuXqAZ5aKpJKPyJZoRTVVVU6mO0JuU1oSQhjD-Gh0xKuqmFmyG7n-6zejdykGPLyBDDHZrvbP4dDA-3EyQcFjhcz-FO8huAHw53LrO5VL7ybrOA75yOZaG6zvXA_4RQ9nPLgzYDXjpxjAGv03G2lsTC1D96yvDzv4wvADv01v0amV8gneP9Rj9Pv_2a3FRLa-_Xy5Ol5WVTOeqoYz3tBO9biQ30AOvWdMwpQjtBRgNijIitBKGMAXUiEYLa7nqubQghObH6GSfO8bwt7wrtxuXbLmBGSBMqVU1KWGcyEJ-epaksmZ1rSUXBf34H7oOUyxfV6jd0EYJTQr1eU_ZGFKKsGrH6DYmbltK2p3CtihsuWiLwgJ_eIycug30B_TJWQG-7oF1yuYGDoCJ2VkPT1liv5TIw8nOQQsDfwBWLK1V</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Park, Ju-Young</creator><creator>Kim, Seung-Woo</creator><creator>Lee, Ja-Kyeong</creator><creator>Im, Weon Bin</creator><creator>Jin, Byung Kwan</creator><creator>Yoon, Sung-Hwa</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20110401</creationdate><title>Simplified Heterocyclic Analogues of Fluoxetine Inhibit Inducible Nitric Oxide Production in Lipopolysaccharide-Induced BV2 Cells</title><author>Park, Ju-Young ; Kim, Seung-Woo ; Lee, Ja-Kyeong ; Im, Weon Bin ; Jin, Byung Kwan ; Yoon, Sung-Hwa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-7123d1b4d9753aede3627728801d4ea9e81204984a028e1a4794cc38d35ce4493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - chemical synthesis</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>BV2 cell</topic><topic>Cell Line</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fluoxetine - analogs & derivatives</topic><topic>Fluoxetine - pharmacology</topic><topic>fluoxetine analogue</topic><topic>Heterocyclic Compounds - chemical synthesis</topic><topic>Heterocyclic Compounds - pharmacology</topic><topic>inducible nitric oxide synthase</topic><topic>Lipopolysaccharides</topic><topic>Mice</topic><topic>microglia</topic><topic>nitric oxide</topic><topic>Nitric Oxide - biosynthesis</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Ju-Young</creatorcontrib><creatorcontrib>Kim, Seung-Woo</creatorcontrib><creatorcontrib>Lee, Ja-Kyeong</creatorcontrib><creatorcontrib>Im, Weon Bin</creatorcontrib><creatorcontrib>Jin, Byung Kwan</creatorcontrib><creatorcontrib>Yoon, Sung-Hwa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Ju-Young</au><au>Kim, Seung-Woo</au><au>Lee, Ja-Kyeong</au><au>Im, Weon Bin</au><au>Jin, Byung Kwan</au><au>Yoon, Sung-Hwa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simplified Heterocyclic Analogues of Fluoxetine Inhibit Inducible Nitric Oxide Production in Lipopolysaccharide-Induced BV2 Cells</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>34</volume><issue>4</issue><spage>538</spage><epage>544</epage><pages>538-544</pages><issn>0918-6158</issn><issn>1347-5215</issn><eissn>1347-5215</eissn><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. 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| subjects | Animals Anti-Inflammatory Agents - chemical synthesis Anti-Inflammatory Agents - pharmacology BV2 cell Cell Line Dose-Response Relationship, Drug Fluoxetine - analogs & derivatives Fluoxetine - pharmacology fluoxetine analogue Heterocyclic Compounds - chemical synthesis Heterocyclic Compounds - pharmacology inducible nitric oxide synthase Lipopolysaccharides Mice microglia nitric oxide Nitric Oxide - biosynthesis Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism RNA, Messenger - metabolism |
| title | Simplified Heterocyclic Analogues of Fluoxetine Inhibit Inducible Nitric Oxide Production in Lipopolysaccharide-Induced BV2 Cells |
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