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

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)493-500
Number of pages8
JournalJournal of Natural Products
Volume85
Issue number3
DOIs
Publication statusPublished - 2022 Mar 25

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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