1. Metabolomic Characterization of a cf. Neolyngbya Cyanobacterium from the South China Sea Reveals Wenchangamide A, a Lipopeptide with In Vitro Apoptotic Potential in Colon Cancer Cells
- Author
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Shuang Li, Shan He, C. Benjamin Naman, Chengcong Zhu, Lijian Ding, Fuad Fares, Naoaki Kurisawa, Haixi Luo, Arihiro Iwasaki, Kiyotake Suenaga, Fuli Tian, Rinat Bar-Shalom, Xiaojun Yan, Dikla Aharonovich, Tal Luzzatto-Knaan, and Gaurav Patial
- Subjects
0301 basic medicine ,Cyanobacteria ,Aquatic Organisms ,China ,wenchangamide ,Colorectal cancer ,natural products ,QH301-705.5 ,Pharmaceutical Science ,South China Sea ,anticancer ,01 natural sciences ,cyanobacteria ,Article ,drug discovery ,03 medical and health sciences ,chemistry.chemical_compound ,Lipopeptides ,Metabolomics ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neolyngbya ,Biology (General) ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Cell Proliferation ,Biological Products ,Natural product ,biology ,010405 organic chemistry ,Drug discovery ,secondary metabolites ,Lipopeptide ,biology.organism_classification ,medicine.disease ,metabolomics ,In vitro ,0104 chemical sciences ,030104 developmental biology ,chemistry ,Biochemistry ,Apoptosis - Abstract
Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A (1). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC50 = 38 μM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1, here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues.
- Published
- 2021