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

C. Benjamin Naman, Jehad Almaliti, Lorene Armstrong, Eduardo J. Caro-Díaz, Marsha L. Pierce, Evgenia Glukhov, Amanda Fenner, Carmenza Spadafora, Hosana M. Debonsi, Pieter C. Dorrestein, Thomas F. Murray, William H. Gerwick

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 gem-dichlorovinylidene moiety, caracolamide 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 μM).

Original languageEnglish (US)
Pages (from-to)2328-2334
Number of pages7
JournalJournal of Natural Products
Volume80
Issue number8
DOIs
StatePublished - Aug 25 2017

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Cyanobacteria
Ion Channels
Cells
Gems
Metabolomics
Calcium Signaling
Alkenes
Drug Discovery
Calcium Channels
Metabolites
Biological Products
Non-Small Cell Lung Carcinoma
Inhibitory Concentration 50
Neurons
Nuclear magnetic resonance
Calcium
Molecules
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Discovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species. / Naman, C. Benjamin; Almaliti, Jehad; Armstrong, Lorene; Caro-Díaz, Eduardo J.; Pierce, Marsha L.; Glukhov, Evgenia; Fenner, Amanda; Spadafora, Carmenza; Debonsi, Hosana M.; Dorrestein, Pieter C.; Murray, Thomas F.; Gerwick, William H.

In: Journal of Natural Products, Vol. 80, No. 8, 25.08.2017, p. 2328-2334.

Research output: Contribution to journalArticle

Naman, CB, Almaliti, J, Armstrong, L, Caro-Díaz, EJ, Pierce, ML, Glukhov, E, Fenner, A, Spadafora, C, Debonsi, HM, Dorrestein, PC, Murray, TF & Gerwick, WH 2017, 'Discovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species', Journal of Natural Products, vol. 80, no. 8, pp. 2328-2334. https://doi.org/10.1021/acs.jnatprod.7b00367
Naman, C. Benjamin ; Almaliti, Jehad ; Armstrong, Lorene ; Caro-Díaz, Eduardo J. ; Pierce, Marsha L. ; Glukhov, Evgenia ; Fenner, Amanda ; Spadafora, Carmenza ; Debonsi, Hosana M. ; Dorrestein, Pieter C. ; Murray, Thomas F. ; Gerwick, William H. / Discovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species. In: Journal of Natural Products. 2017 ; Vol. 80, No. 8. pp. 2328-2334.
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AU - Spadafora, Carmenza

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