Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596639
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Isolation, structure elucidation, and total synthesis of an N-methylated tetrapeptide from a Panamanian marine cyanobacterium

KT Ahmed
1   Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, 600 Forbes Ave. Pittsburgh, PA, 15282, USA
,
C Gayathri
3   Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA, 15213, USA
,
L Pineda
2   Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), City of Knowledge, Apartado 0816 – 02852, Panama City, Panama
,
C Spadafora
2   Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), City of Knowledge, Apartado 0816 – 02852, Panama City, Panama
,
R Gil
3   Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA, 15213, USA
,
WH Gerwick
4   Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92037, USA
,
KJ Tidgewell
1   Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, 600 Forbes Ave. Pittsburgh, PA, 15282, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

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As part of the Panama ICBG efforts to discover novel compounds to be used for the treatment of tropical diseases and cancer, a cyanobacterial extract was shown to have activity against the Trypanosoma cruzi and Plasmodium falciparum parasites. An organic extract was made from an orange cyanobacterium collected in the Portobelo National Park on the Caribbean side of Panama. The crude extract was fractionated into nine fractions using silica gel chromatography and screened for activity against tropical parasites (T. cruzi, L. donavani, P. falciparum) and cancer cell cytotoxicity. One of these subfractions showed 75% inhibition of growth of T. cruzi with greater activity (97%) against P. falciparum. Further purification using Sep-Pak, gave several fractions with selective activity against malria (> 90%) and a fraction that possessed roughly equipotent ˜80% inhibition of T. cruzi and P. falciparum. The malaria selective fractions were shown to possess a known compound while dereplication of the other fraction showed no known compounds present. HPLC purification resulted in identification of a novel N-methylated tetrapeptide. This tetrapeptide was given the trivial name naranjamide and its structure determined using 1- and 2-D NMR and LC-MS-MS. To confirm configuration and activity, a total synthesis of the compound is being undertaken. In addition to the natural product, analogues with variable N-methylation are being synthesized and will be screened for activity. Isolation, structure elucidation, and total synthesis of naranjamide have been undertaken.

Acknowledgements: The authors would like to acknowledge the following funding sources: ICBG grant (U01TW006634) to WHG and ASP Research Starter Grant to KT. We would also like to acknowledge the Autoridad Nacional del Ambiente (ANAM) and Panama for allowing us to collect samples in Panama.

Keywords: Chagas' disease, malaria, marine natural product, total synthesis, cyanobacteria.