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Mooreamide A: A Cannabinomimetic Lipid from the Marine Cyanobacterium Moorea bouillonii

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Lipids

Abstract

Bioassay-guided fractionation of a collection of Moorea bouillonii from Papua New Guinea led to the isolation of a new alkyl amide, mooreamide A (1), along with the cytotoxic apratoxins A–C and E. The planar structure of 1 was elucidated by NMR spectroscopy and mass spectrometry analysis. Structural homology between mooreamide A and the endogenous cannabinoid ligands, anandamide, and 2-arachidonoyl glycerol inspired its evaluation against the neuroreceptors CB1 and CB2. Mooreamide A was found to possess relatively potent and selective ligand binding activity to CB1 (K 1 = 0.47 µM) versus CB2 (K 1 > 25 µM). This represents the most potent marine-derived CB1 ligand described to date and adds to the growing family of marine metabolites that exhibit cannabinomimetic activity.

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Abbreviations

2-AG:

2-Arachidonoyl glycerol

AEA:

Anandamide

CDCl3 :

Deuterated chloroform

CH2Cl2 :

Dichloromethane

CNS:

Central nervous system

COSY:

Correlation spectroscopy

ECS:

Endocannabinoid system

EtOAc:

Ethyl acetate

ESIMS:

Electrospray ionization mass spectrometry

FT:

Fourier transform

GPCR:

G protein-coupled receptor

HMBC:

Heteronuclear multiple bond correlation

HPLC:

High performance liquid chromatography

HR:

High resolution

HSQC:

Heteronuclear single quantum correlation

IR:

Infrared

LR:

Low resolution

MeCN:

Acetonitrile

MeOH:

Methanol

NMR:

Nuclear magnetic resonance

NOESY:

Nuclear Overhauser effect spectroscopy

NP:

Normal phase

OLS:

Olefin synthase

RP:

Reverse phase

SAM:

S-Adenosyl methionine

SCUBA:

Self-contained underwater breathing apparatus

SPE:

Solid phase extraction

UV:

Ultraviolet

Wt:

Weight

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Acknowledgments

We thank the government of Papua New Guinea for the permission to collect the cyanobacterial specimens. We thank the UCSD Chemistry and Biochemistry mass spectrometry facilities for their analytical services. The 500 MHz NMR 13C XSens cold probe was supported by NSF CHE-0741968. We also acknowledge The Growth Regulation & Oncogenesis Training Grant NIH/NCI (T32A009523-24) for a fellowship to E. M., and NIH Grants (CA100851, NS053398) for support of the research.

Author information

Authors and Affiliations

  1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, 92093, USA

    Emily Mevers & William H. Gerwick

  2. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, USA

    Emily Mevers

  3. Discipline of Pharmacology, School of Medicine and Health Sciences, University of Papua New Guinea, National Capital District, Port Moresby, Papua New Guinea

    Teatulohi Matainaho

  4. Institute of Biomolecular Chemistry, National Research Council, 80078, Pozzuoli, Italy

    Marco Allara’ & Vincenzo Di Marzo

  5. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA

    William H. Gerwick

Authors
  1. Emily Mevers
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  2. Teatulohi Matainaho
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  3. Marco Allara’
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  4. Vincenzo Di Marzo
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  5. William H. Gerwick
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Corresponding author

Correspondence to William H. Gerwick.

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Mevers, E., Matainaho, T., Allara’, M. et al. Mooreamide A: A Cannabinomimetic Lipid from the Marine Cyanobacterium Moorea bouillonii . Lipids 49, 1127–1132 (2014). https://doi.org/10.1007/s11745-014-3949-9

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  • DOI: https://doi.org/10.1007/s11745-014-3949-9

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