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Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142
JBIR-141 (1) and JBIR-142 (2) were discovered as potent Foxo3a inhibitors that consist of three quite unique substructures, a 1-((dimethylamino)ethyl)-5-methyl-4,5-dihydrooxazole-4-carboxylic acid that is originated from Ala-Thr amino acid residues, a 3-acetoxy-4-amino-7-(hydroxy(nitroso)amino)-2...
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| Published in: | Organic letters 2015-11, Vol.17 (21), p.5476-5479 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
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| cites | cdi_FETCH-LOGICAL-a411t-a509022d10330d65bdb630077d51a9e0777bc78c1a0250e475c793e3f8eddb883 |
| container_end_page | 5479 |
| container_issue | 21 |
| container_start_page | 5476 |
| container_title | Organic letters |
| container_volume | 17 |
| creator | Kawahara, Teppei Kagaya, Noritaka Masuda, Yuichi Doi, Takayuki Izumikawa, Miho Ohta, Kumiko Hirao, Atsushi Shin-ya, Kazuo |
| description | JBIR-141 (1) and JBIR-142 (2) were discovered as potent Foxo3a inhibitors that consist of three quite unique substructures, a 1-((dimethylamino)ethyl)-5-methyl-4,5-dihydrooxazole-4-carboxylic acid that is originated from Ala-Thr amino acid residues, a 3-acetoxy-4-amino-7-(hydroxy(nitroso)amino)-2,2-dimethylheptanoic acid, and an α-acyl tetramic acid fused with a 2-methylpropan-1-ol moiety. Their structures involving absolute configurations were determined by spectroscopic data, chemical degradation, anisotropy methods, and LC–MS analyses of diastereomeric derivatives. Compounds 1 and 2 exhibited specific inhibition against Foxo3a transcriptional activity with IC50 values of 23.1 and 166.2 nM, respectively. |
| doi_str_mv | 10.1021/acs.orglett.5b02842 |
| format | article |
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Compounds 1 and 2 exhibited specific inhibition against Foxo3a transcriptional activity with IC50 values of 23.1 and 166.2 nM, respectively.</description><subject>Animals</subject><subject>Forkhead Box Protein O3</subject><subject>Forkhead Transcription Factors - antagonists & inhibitors</subject><subject>Inhibitory Concentration 50</subject><subject>Molecular Structure</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Oxadiazoles - chemistry</subject><subject>Oxadiazoles - isolation & purification</subject><subject>Oxadiazoles - pharmacology</subject><subject>Porifera</subject><subject>Streptomyces - chemistry</subject><issn>1523-7060</issn><issn>1523-7052</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kF1LwzAUhoMobk5_gSC99MJuJ0nTtOCNDqeTyUD0OqRNOjO6ZiYt6L83Y90uvTofvO_5eBC6xjDGQPBEln5s3arWbTtmBZAsISdoiBmhMQdGTo95CgN04f0aAIdOfo4GJE1ymmT5EN3P7I-lMpo3X6YwrXU-slX0ZkpnCyPraOnMyjR30evj_D3GCY5kow4FuURnlay9vurjCH3Onj6mL_Fi-TyfPiximWDcxpJBDoQoDJSCSlmhipQCcK4YlrkOCS9KnpVYAmGgE85KnlNNq0wrVWQZHaHb_dyts9-d9q3YGF_qupaNtp0XmFPMMxbOC1K6l4YHvHe6EltnNtL9Cgxih00EbKLHJnpswXXTL-iKjVZHz4FTEEz2gp17bTvXhH__HfkH_0F3ew</recordid><startdate>20151106</startdate><enddate>20151106</enddate><creator>Kawahara, Teppei</creator><creator>Kagaya, Noritaka</creator><creator>Masuda, Yuichi</creator><creator>Doi, Takayuki</creator><creator>Izumikawa, Miho</creator><creator>Ohta, Kumiko</creator><creator>Hirao, Atsushi</creator><creator>Shin-ya, Kazuo</creator><general>American Chemical Society</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>7X8</scope></search><sort><creationdate>20151106</creationdate><title>Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142</title><author>Kawahara, Teppei ; Kagaya, Noritaka ; Masuda, Yuichi ; Doi, Takayuki ; Izumikawa, Miho ; Ohta, Kumiko ; Hirao, Atsushi ; Shin-ya, Kazuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a411t-a509022d10330d65bdb630077d51a9e0777bc78c1a0250e475c793e3f8eddb883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Forkhead Box Protein O3</topic><topic>Forkhead Transcription Factors - antagonists & inhibitors</topic><topic>Inhibitory Concentration 50</topic><topic>Molecular Structure</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Oxadiazoles - chemistry</topic><topic>Oxadiazoles - isolation & purification</topic><topic>Oxadiazoles - pharmacology</topic><topic>Porifera</topic><topic>Streptomyces - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawahara, Teppei</creatorcontrib><creatorcontrib>Kagaya, Noritaka</creatorcontrib><creatorcontrib>Masuda, Yuichi</creatorcontrib><creatorcontrib>Doi, Takayuki</creatorcontrib><creatorcontrib>Izumikawa, Miho</creatorcontrib><creatorcontrib>Ohta, Kumiko</creatorcontrib><creatorcontrib>Hirao, Atsushi</creatorcontrib><creatorcontrib>Shin-ya, Kazuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Organic letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawahara, Teppei</au><au>Kagaya, Noritaka</au><au>Masuda, Yuichi</au><au>Doi, Takayuki</au><au>Izumikawa, Miho</au><au>Ohta, Kumiko</au><au>Hirao, Atsushi</au><au>Shin-ya, Kazuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142</atitle><jtitle>Organic letters</jtitle><addtitle>Org. Lett</addtitle><date>2015-11-06</date><risdate>2015</risdate><volume>17</volume><issue>21</issue><spage>5476</spage><epage>5479</epage><pages>5476-5479</pages><issn>1523-7060</issn><eissn>1523-7052</eissn><abstract>JBIR-141 (1) and JBIR-142 (2) were discovered as potent Foxo3a inhibitors that consist of three quite unique substructures, a 1-((dimethylamino)ethyl)-5-methyl-4,5-dihydrooxazole-4-carboxylic acid that is originated from Ala-Thr amino acid residues, a 3-acetoxy-4-amino-7-(hydroxy(nitroso)amino)-2,2-dimethylheptanoic acid, and an α-acyl tetramic acid fused with a 2-methylpropan-1-ol moiety. Their structures involving absolute configurations were determined by spectroscopic data, chemical degradation, anisotropy methods, and LC–MS analyses of diastereomeric derivatives. Compounds 1 and 2 exhibited specific inhibition against Foxo3a transcriptional activity with IC50 values of 23.1 and 166.2 nM, respectively.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>26493489</pmid><doi>10.1021/acs.orglett.5b02842</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1523-7060 |
| ispartof | Organic letters, 2015-11, Vol.17 (21), p.5476-5479 |
| issn | 1523-7060 1523-7052 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1731785141 |
| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Animals Forkhead Box Protein O3 Forkhead Transcription Factors - antagonists & inhibitors Inhibitory Concentration 50 Molecular Structure Nuclear Magnetic Resonance, Biomolecular Oxadiazoles - chemistry Oxadiazoles - isolation & purification Oxadiazoles - pharmacology Porifera Streptomyces - chemistry |
| title | Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142 |
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