TY - JOUR
T1 - Targeted Discovery of Amantamide B, an Ion Channel Modulating Nonapeptide from a South China Sea Oscillatoria Cyanobacterium
AU - Li, Te
AU - Xi, Chuchu
AU - Yu, Yiyi
AU - Wang, Ning
AU - Wang, Xiao
AU - Iwasaki, Arihiro
AU - Fang, Fang
AU - Ding, Lijian
AU - Li, Shuang
AU - Zhang, Weiyan
AU - Yuan, Ye
AU - Wang, Tingting
AU - Yan, Xiaojun
AU - He, Shan
AU - Cao, Zhengyu
AU - Naman, C. Benjamin
N1 - Funding Information:
This study was supported by the Ministry of Science and Technology of China National Key Research and Development Program (MOST; grant 2018YFC0310900 to X.Y., S.H., and C.B.N.), the National Natural Science Foundation of China (NSFC; grant 81850410553 and 82050410451 to C.B.N.), the National 111 Project of China (D16013), and the Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Development Fund. We thank Z. Long, D. Li, and D. Huo of the Xisha Marine Science Comprehensive Experimental Station, South China Sea Institute of Oceanology, Chinese Academy of Sciences, for their assistance. We appreciate Dr. X. Cao of Zhejiang University of Technology for the acquisition of HRESIMS data, Dr. H. Zhu of Shanghai Institute of Organic Sciences for assistance collecting NMR data, and Dr. C. Lu of Shanghai Institute of Organic Sciences for help in obtaining OR data. We thank Dr. R. T. Williamson at University of North Carolina Wilmington for thoughtful conversation and Dr. H. Luesch at University of Florida for helpful discussion and sharing of raw NMR data files for amantamide ( 2 ).
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/3/25
Y1 - 2022/3/25
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jnatprod.1c00983
DO - 10.1021/acs.jnatprod.1c00983
M3 - Article
C2 - 34986303
AN - SCOPUS:85122784209
VL - 85
SP - 493
EP - 500
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 3
ER -