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Mar. Drugs 2019, 17(2), 83; https://doi.org/10.3390/md17020083

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

1
Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA
2
Research Center for Oceanography, Indonesian Institute of Sciences, Jl. Pasir Putih I, Ancol Timur, Jakarta 14430, Indonesia
3
State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, Shenzhen 518055, China
4
QianYan Pharmatech Limited, Shenzhen 518172, China
5
Smithsonian Marine Station, 701 Seaway Drive, Fort Pierce, FL 34949, USA
*
Author to whom correspondence should be addressed.
Received: 29 December 2018 / Revised: 16 January 2019 / Accepted: 18 January 2019 / Published: 1 February 2019
(This article belongs to the Special Issue Compounds from Cyanobacteria II)
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Abstract

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. View Full-Text
Keywords: marine cyanobacteria; cyclic depsipeptides; acyl migration; anticancer; apoptosis marine cyanobacteria; cyclic depsipeptides; acyl migration; anticancer; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Luo, D.; Putra, M.Y.; Ye, T.; Paul, V.J.; Luesch, H. Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria. Mar. Drugs 2019, 17, 83.

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