2. Academic Validation
  3. Targeted Discovery of Amantamide B, an Ion Channel Modulating Nonapeptide from a South China Sea Oscillatoria Cyanobacterium

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

  • J Nat Prod. 2022 Mar 25;85(3):493-500. doi: 10.1021/acs.jnatprod.1c00983.
Te Li 1 2,  Chuchu Xi 3,  Yiyi Yu 3,  Ning Wang 4,  Xiao Wang 5,  Arihiro Iwasaki 6,  Fang Fang 2,  Lijian Ding 2,  Shuang Li 2,  Weiyan Zhang 2,  Ye Yuan 2,  Tingting Wang 2,  Xiaojun Yan 2,  Shan He 2,  Zhengyu Cao 3,  C Benjamin Naman 2
Affiliations

Affiliations

  • 1 School of Marine Science, Ningbo University, Ningbo, Zhejiang 315800, People's Republic of China.
  • 2 Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315800, People's Republic of China.
  • 3 State Key Laboratory of Natural Medicines & Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, People's Republic of China.
  • 4 Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, People's Republic of China.
  • 5 Department of Pathology and Pathogen Biology, College of Medicine, Ningbo University, Ningbo, Zhejiang 315211, People's Republic of China.
  • 6 Department of Chemistry, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
PMID: 34986303 DOI: 10.1021/acs.jnatprod.1c00983
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 IC50 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.

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