Discovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species

TitleDiscovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species
Publication TypeJournal Article
Year of Publication2017
AuthorsNaman C.B, Almaliti J., Armstrong L., Caro-Diaz E.J, Pierce M.L, Glukhov E., Fenner A., Spadafora C., Debonsi H.M, Dorrestein PC, Murray T.F, Gerwick WH
JournalJournal of Natural Products
Volume80
Pagination2328-2334
Date Published2017/08
Type of ArticleArticle
ISBN Number0163-3864
Accession NumberWOS:000408702600017
Keywords1,1-dihaloolefins; assemblage; fatty-acid; isotactic polymethoxy-1-alkenes; neocortical neurons; toxins; trace amines
Abstract

A recent untargeted metabolomics investigation into the chemical profile of 10 organic extracts from cf. Symploca spp. revealed several interesting chemical leads for further natural product drug discovery. Subsequent target directed isolation efforts with one of these, a Panamanian marine cyanobacterium cf. Symploca sp., yielded a phenethylamide metabolite that terminates in a relatively rare gemdichlorovinylidene moiety, caracolarnide A (1), along with a known isotactic polymethoxy-1-alkene (2). Detailed NMR and HRESIMS analyses were used to determine the structures of these molecules, and compound 1 was confirmed by a three step synthesis. Pure compound 1 was shown to have in vitro calcium influx and calcium channel oscillation modulatory activity when tested as low as 10 pM using cultured murine cortical neurons, but was not cytotoxic to NCI-H460 human non-small-cell lung cancer cells in vitro (IC50 > 10 mu M).

DOI10.1021/acs.jnatprod.7b00367
Short TitleJ. Nat. Prod.
Student Publication: 
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