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Corresponding Author: julia.kubanek@biosci.gatech.edu

The authors thank the Government of Fiji and the customary fishing right owners for permission to perform research in their territorial waters, and M.E. Hay and W. Aalsberberg for management of the project.

We thank M.E. Hay, D. Rasher, K. Soape, and K. Feussner for collection of algal samples; D.E Bostwick and C. Sullards for mass spectrometric analyses; L.T. Gelbaum for NMR assistance; N.V. Hud and S. Karunakaran for ECD spectroscopy measurement; J. Mathew-Valayil, K. Syhapanha, and S. Engel for antimicrobial assays; and A.M. Sweeney-Jones for comments to improve the manuscript.

We are especially appreciative of the leadership of the Georgia Institute of Technology for investing in new NMR capabilities in 2016, making this research possible.

The authors declare no competing financial interest.

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Research Funding:

This work was supported by ICBG Grant U19-TW007401 from the U.S. National Institutes of Health.

Staphylococcus aureus, Strain HIP5827, NR-45858 was provided by the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) for distribution by BEI Resources, NIAID, NIH.

Enterococcus faecium, Strain E0164, NR-31915 was obtained through BEI Resources, NIAID, NIH as part of the Human Microbiome Project.

Iodinated Meroditerpenes from a Red Alga Callophycus sp.

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Journal Title:

Journal of Organic Chemistry Research

Volume:

Volume 82, Number 8

Publisher:

, Pages 4160-4169

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Unique iodine-containing meroditerpenes iodocallophycoic acid A (1) and iodocallophycols A-D (2-5) were discovered from the Fijian red alga Callophycus sp. Because flexibility of the molecular skeleton impaired full characterization of relative stereochemistries by NMR spectroscopy, a DFT-based theoretical model was developed to derive relevant interproton distances which were compared to those calculated from NOE measurements, yielding the relative stereochemistries. The correct 2S,6S,7S,10S,14S enantiomers were then identified by comparison of theoretical and experimental ECD spectra. Biological activities of these iodinated and brominated meroditerpenes and additional new, related bromophycoic acid F (6) and bromophycoic acid A methyl ester (7), were evaluated for relevant human disease targets. Iodocallophycoic acid A (1) showed moderate antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) with MIC values of 1.4 and 2.2 μg mL -1 , respectively. It also potentiated the anti-MRSA activity of oxacillin in a synergistic fashion, resulting in an 8-fold increase in oxacillin potency, for a MIC of 16 μg mL -1 .

Copyright information:

© 2017 American Chemical Society.

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