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Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria

Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection of marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular ester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered compound via acyl migrati...

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Autores principales: Luo, Danmeng, Putra, Masteria Y., Ye, Tao, Paul, Valerie J., Luesch, Hendrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410412/
https://www.ncbi.nlm.nih.gov/pubmed/30717076
http://dx.doi.org/10.3390/md17020083
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author Luo, Danmeng
Putra, Masteria Y.
Ye, Tao
Paul, Valerie J.
Luesch, Hendrik
author_facet Luo, Danmeng
Putra, Masteria Y.
Ye, Tao
Paul, Valerie J.
Luesch, Hendrik
author_sort Luo, Danmeng
collection PubMed
description Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection of marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular ester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered compound via acyl migration at the 1,3-diol unit, and the transformation product was named lagunamide D’. The planar structures of both compounds were elucidated using a combination of nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectroscopy (HRMS). The absolute configurations were determined on the basis of enantioselective analysis, modified Mosher’s analysis, Kishi NMR database, and direct comparison with lagunamide A, a structure closely resembling lagunamide D. Lagunamides A and D displayed low-nanomolar antiproliferative activity against A549 human lung adenocarcinoma cells, while the structural transformation from the 26-membered lagunamide D macrocycle to the 24-membered ring structure for lagunamide D’ led to a 9.6-fold decrease in activity. Lagunamide D also displayed potent activity in triggering apoptosis in a dose- and time-dependent manner. Further investigation on the mechanism of action of the lagunamide scaffold is needed to fully explore its therapeutic potential as an anticancer agent.
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spelling pubmed-64104122019-03-29 Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria Luo, Danmeng Putra, Masteria Y. Ye, Tao Paul, Valerie J. Luesch, Hendrik Mar Drugs Article Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection of marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular ester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered compound via acyl migration at the 1,3-diol unit, and the transformation product was named lagunamide D’. The planar structures of both compounds were elucidated using a combination of nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectroscopy (HRMS). The absolute configurations were determined on the basis of enantioselective analysis, modified Mosher’s analysis, Kishi NMR database, and direct comparison with lagunamide A, a structure closely resembling lagunamide D. Lagunamides A and D displayed low-nanomolar antiproliferative activity against A549 human lung adenocarcinoma cells, while the structural transformation from the 26-membered lagunamide D macrocycle to the 24-membered ring structure for lagunamide D’ led to a 9.6-fold decrease in activity. Lagunamide D also displayed potent activity in triggering apoptosis in a dose- and time-dependent manner. Further investigation on the mechanism of action of the lagunamide scaffold is needed to fully explore its therapeutic potential as an anticancer agent. MDPI 2019-02-01 /pmc/articles/PMC6410412/ /pubmed/30717076 http://dx.doi.org/10.3390/md17020083 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Luo, Danmeng
Putra, Masteria Y.
Ye, Tao
Paul, Valerie J.
Luesch, Hendrik
Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria
title Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria
title_full Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria
title_fullStr Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria
title_full_unstemmed Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria
title_short Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria
title_sort isolation, structure elucidation and biological evaluation of lagunamide d: a new cytotoxic macrocyclic depsipeptide from marine cyanobacteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410412/
https://www.ncbi.nlm.nih.gov/pubmed/30717076
http://dx.doi.org/10.3390/md17020083
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