Targeted Discovery of Amantamide B, an Ion Channel Modulating Nonapeptide from a South China Sea Oscillatoria Cyanobacterium.
Te LiChuchu XiYiyi YuNing WangXiao WangArihiro IwasakiFang FangLi-Jian DingShuang LiWeiyan ZhangYe YuanTingting WangXiaojun YanShan HeZheng-Yu CaoC Benjamin NamanPublished in: Journal of natural products (2022)
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.
Keyphrases
- endothelial cells
- induced apoptosis
- cell cycle arrest
- high resolution
- signaling pathway
- oxidative stress
- ms ms
- small molecule
- cancer therapy
- spinal cord
- single molecule
- pluripotent stem cells
- endoplasmic reticulum stress
- induced pluripotent stem cells
- diffuse large b cell lymphoma
- climate change
- risk assessment
- working memory
- drug delivery
- high performance liquid chromatography
- single cell
- blood brain barrier
- water soluble