Targeted Discovery of Amantamide B, an Ion Channel Modulating Nonapeptide from a South China Sea Oscillatoria Cyanobacterium

Abstract

Amantamide B (1) is a new linear nonapeptide analogue of the cyanobacterial natural product amantamide A (2), and both have methyl ester and butanamide termini. These compounds were discovered in this study from the organic extract of a tropical marine filamentous cyanobacterium, Oscillatoria sp., collected around the Paracel Islands in the South China Sea. The use of LC-MS/MS molecular networking for sample prioritization and as an analytical dereplication tool facilitated the targeted isolation of 1 and 2. These molecules were characterized by spectroscopy and spectrometry, and configurational assignments were determined using chemical degradation and chiral-phase HPLC analysis. Compounds 1 and 2 modulated spontaneous calcium oscillations without notable cytotoxicity at 10 μM in short duration in vitro testing on primary cultured neocortical neurons, a model system that evaluates neuronal excitability and/or the potential activity on Ca 2+ signaling. Both molecules were also found to be moderately cytotoxic in longer duration bioassays, with in vitro IC 50 values of 1−10 μM against CCRF-CEM human T lymphoblastoid cells and U937 human histiocytic lymphoma cells. These formerly undiscovered bioactivities of known compound 2 expand upon its previously reported function as a selective CXCR7 agonist among 168 GPCR targets.

Marine natural products

“…Notably, the 1-amidino-3-(2-aminoethyl)-3-pyrroline amino acid moiety in 239 was shown to enhance activity and selectivity in three human trypsin isoforms over a hundred-fold compared to 240 that contained a 4-amidinobutylamide moiety. Other new cyanobacterial-sourced peptides included the linear peptides amantamide B 241 from Oscillatoria sp., identified via a MS/MS-based molecular networking approach, 97 acetylene-containing odookeanynes A 242 and B 243 from Okeania sp., 98 as well as the cyclic depsipeptides triproamide 244 and pemukainalides A 245 and B 246 isolated from Symploca hydnoides . 99…”

Xinghamide A, a New Cyclic Nonapeptide Found in Streptomyces xinghaiensis

“…The agar media covered with S. xinghaiensis were cut into 1 cm × 1 cm pieces and extracted with ethyl acetate followed by methanol. The dried methanol extract (24 g) was loaded onto a prepacked SPE-C18 column (S*Pure, Singapore) and stepwise eluted (20,40,60,80, and 100% aqueous methanol). The targeted compound was eluted with 40% aqueous methanol (5.8 g), and the fraction was further purified with semipreparative LC-MS instruments.…”

“…Also, amantamides A and B showed moderate cytotoxicity against CCRF-CEM human T lymphoblast cells and U937 human histiocytic lymphoma cells. Amantamides A and B presented IC 50 values of 8.3 µM and 5.6 µM, respectively, against CCRF-CEM cells, while A and B showed an IC 50 of 6.1 µM and 7.3 µM, respectively, against U937 cells [20]. Marine-derived nonapeptides have diverse activities, including vasopressin-like activity and cytotoxicity, and could be the candidates of bioactive materials (Figure 1 and Table 1).…”

Nucleobase-Coupled Xanthones with Anti-ROS Effects from Marine-Derived Fungus Aspergillus sydowii

“…Using liquid chromatography–tandem mass spectrometry (LC–MS/MS) data and the Global Natural Product Social Molecular Networking (GNPS) library for chemical screening of metabolic profiles is a promising method for guiding targeted isolation from crude extracts. , Additionally, genome-based screening offers another approach for identifying potential natural products at the gene level. , In this study, a genome sequencing-coupled LC–MS/MS molecular networking approach was used to screen marine-derived fungal strains from an in-house library. As a result, the fungus Aspergillus sydowii PKU374 was selected for chemical examination due to its production of xanthone-related metabolites.…”