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

Te Li, Chuchu Xi, Yiyi Yu, Ning Wang, Xiao Wang, Arihiro Iwasaki, Fang Fang, Lijian Ding, Shuang Li, Weiyan Zhang, Ye Yuan, Tingting Wang, Xiaojun Yan, Shan He, Zhengyu Cao, C. Benjamin Naman

研究成果: Article査読

抄録

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 Ca2+signaling. Both molecules were also found to be moderately cytotoxic in longer duration bioassays, with in vitro IC50values 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.

本文言語English
ページ(範囲)493-500
ページ数8
ジャーナルJournal of Natural Products
85
3
DOI
出版ステータスPublished - 2022 3月 25

ASJC Scopus subject areas

  • 分析化学
  • 分子医療
  • 薬理学
  • 薬科学
  • 創薬
  • 補完代替医療
  • 有機化学

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