Pagoamide A, a Cyclic Depsipeptide Isolated from a Cultured Marine Chlorophyte, Derbesia sp., Using MS/MS-Based Molecular Networking

Abstract

A thiazole-containing cyclic depsipeptide with 11 amino acid residues, named pagoamide A (1), was isolated from laboratory cultures of a marine Chlorophyte, Derbesia sp. This green algal sample was collected from America Samoa, and pagoamide A was isolated using guidance by MS/MSbased molecular networking. Cultures were grown in a lightand temperature-controlled environment and harvested after several months of growth. The planar structure of pagoamide A (1) was characterized by detailed 1D and 2D NMR experiments along with MS and UV analysis. The absolute configurations of its amino acid residues were determined by advanced Marfey's analysis following chemical hydrolysis and hydrazinolysis reactions. Two of the residues in pagoamide A (1), phenylalanine and serine, each occurred twice in the molecule, once in the D-and once in the L-configuration. The biosynthetic origin of pagoamide A (1) was considered in light of other natural products investigations with coenocytic green algae.

Exploring the Chemical Space of Macro- and Micro-Algae Using Comparative Metabolomics

“…This approach, coupled with approaches such as molecular networking, has been utilised in drug discovery, including the discovery of tutuilamides A–C, from a marine cyanobacterium, with potent elastase inhibition (IC 50 1–5 nM) and anticancer activity against lung H-460 cells [ 17 ]. Comparative metabolomics using the Global Natural Products Social (GNPS) molecular networking [ 18 ] platform led to the discovery of several new metabolites from cyanobacteria and microalgae, including yuvalamide A [ 19 ], pagoamide A [ 20 ], and palstimolide A, which exhibited strong anti-parasitic activity (IC 50 of 223 nM against malaria and 4.67 μM against leishmaniasis) [ 21 ].…”

Total Synthesis of Pagoamide A

“…The optical rotation of the synthetic product 1 = +8.0 ( c 0.1, MeOH), was in close agreement with the value reported in the literature for natural pagoamide A = +5.5 ( c 0.1, MeOH). Spectral data, including 1 H-NMR, 13 C-NMR, were collected for both the natural and synthetic sample ( 1 ) and found to be in full agreement ( Table 2 ) [ 1 ], while the synthetic 1a showed remarkable discrepancies in spectral data as compared to natural pagoamide A, which unambiguously confirmed the original assignments of natural pagoamide A.…”

“…Very recently, Gerwick and co-workers described the structure of pagoamide A [ 1 ], a thiazole-containing cyclic depsipeptide isolated from the metabolites of a marine Chlorphyte, Derbesia sp., which was collected from the shallow coastal waters near American Samoa and cultured in the laboratory. Preliminary biological tests revealed that pagoamide A had no cytotoxicity against H-460 human lung cancer cells.…”

Combination of Molecular Networking and LC-MS/MS Profiling in Investigating the Interrelationships between the Antioxidant and Antimicrobial Properties of Curculigo latifolia

“…The MS and MS/MS data of C. latifolia was subjected to MN analysis. The mass spectroscopic data were transformed into the mzXML format [59], and then processed on an online platform (http://gnps.ucsd.edu, accessed on 21 August 2019) according to a MN method [60]. The detailed metabolite information of the crude extract can be accessed via https://gnps.ucsd.edu/ProteoSAFe/libraries.jsp, accessed on 6 June 2021 and https://pubchem.ncbi.nlm.nih.gov/, accessed on 6 June 2021 (crude extract + references).…”