{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:28:01Z","timestamp":1785461281298,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T00:00:00Z","timestamp":1450742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T00:00:00Z","timestamp":1450742400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"National Institute of Health","award":["SC1GM084708"],"award-info":[{"award-number":["SC1GM084708"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lipids"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The novel fatty acids (2<jats:italic>R<\/jats:italic>,5<jats:italic>Z<\/jats:italic>,9<jats:italic>Z<\/jats:italic>)\u20102\u2010methoxy\u201025\u2010methyl\u20105,9\u2010hexacosadienoic acid (<jats:bold>1a<\/jats:bold>) and (2<jats:italic>R<\/jats:italic>,5<jats:italic>Z<\/jats:italic>,9<jats:italic>Z<\/jats:italic>)\u20102\u2010methoxy\u201024\u2010methyl\u20105,9\u2010hexacosadienoic acid (<jats:bold>1b<\/jats:bold>) were isolated in 80 % purity from the Caribbean sponge <jats:italic>Asteropus niger<\/jats:italic> by chloroform\/methanol extraction followed by solvent partitioning and silica gel column chromatography. The compounds were characterized by utilizing a combination of gas chromatography\u2010mass spectrometry, nuclear magnetic resonance, and circular dichroism. Acids <jats:bold>1a<\/jats:bold> and <jats:bold>1b<\/jats:bold> were not detected in the phospholipids (PtdCho and PtdIns) of the sponge, but rather as free FA and possibly in glycosylceramides. The mixtures of <jats:bold>1a<\/jats:bold> and <jats:bold>1b<\/jats:bold> displayed cytotoxicity towards THP\u20101 and HepG2 cells with EC<jats:sub>50's<\/jats:sub> between 41 and 35 \u03bcg\/mL. Apoptosis was not the preferred mode of cell death induced by <jats:bold>1a<\/jats:bold>\u2013<jats:bold>1b<\/jats:bold> in the THP\u20101 cells. This implies other types of cytotoxicity mechanisms, such as membrane disruption and\/or the inhibition (EC<jats:sub>50<\/jats:sub> = 1.8 \u03bcg\/mL) of the human topoisomerase IB enzyme (<jats:italic>h<\/jats:italic>TopIB), with a mechanism of inhibition different from the one displayed by camptothecin (CPT). In a separate experiment, the mixture of <jats:bold>1a<\/jats:bold> and <jats:bold>1b<\/jats:bold> also displayed cytotoxicity towards <jats:italic>ex vivo<\/jats:italic> mouse splenocytes infected with <jats:italic>Leishmania infantum<\/jats:italic> amastigotes (IC<jats:sub>50<\/jats:sub> = 0.17 mg\/mL) and free living promastigotes (IC<jats:sub>50<\/jats:sub> = 0.34 mg\/mL). It was also found that the FA were inhibitory of the <jats:italic>Leishmania<\/jats:italic> topoisomerase IB (<jats:italic>L<\/jats:italic>TopIB) with an EC<jats:sub>50<\/jats:sub> = 5.1 \u03bcg\/mL. Taken together, <jats:bold>1a<\/jats:bold> and <jats:bold>1b<\/jats:bold> represent a new class of FA with potential as TopIB inhibitors that preferentially inhibit <jats:italic>h<\/jats:italic>TopIB over <jats:italic>L<\/jats:italic>TopIB.<\/jats:p>","DOI":"10.1007\/s11745-015-4114-9","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T02:42:45Z","timestamp":1450752165000},"page":"245-256","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Novel Very Long\u2010Chain \u03b1\u2010Methoxylated \u03945,9 Fatty Acids from the Sponge <i>Asteropus niger<\/i> Are Effective Inhibitors of Topoisomerases IB"],"prefix":"10.1002","volume":"51","author":[{"given":"N\u00e9stor M.","family":"Carballeira","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Puerto Rico Rio Piedras Campus 00931\u20103346 San Juan PR PO Box 23346 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nashbly","family":"Montano","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Puerto Rico Rio Piedras Campus 00931\u20103346 San Juan PR PO Box 23346 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.","family":"Amador","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Puerto Rico Rio Piedras Campus 00931\u20103346 San Juan PR PO Box 23346 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abimael D.","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Puerto Rico Rio Piedras Campus 00931\u20103346 San Juan PR PO Box 23346 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail Y.","family":"Golovko","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences University of North Dakota Grand Forks ND 58202\u20109037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana A.","family":"Golovko","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences University of North Dakota Grand Forks ND 58202\u20109037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa M.","family":"Reguera","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Le\u00f3n Campus de Vegazana s\/n Le\u00f3n 24071 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"\u00c1lvarez\u2010Velilla","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Le\u00f3n Campus de Vegazana s\/n Le\u00f3n 24071 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Bala\u00f1a\u2010Fouce","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Le\u00f3n Campus de Vegazana s\/n 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