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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6410412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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