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

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.

Marine natural products

“…ferment that displayed in vitro apoptotic potential towards colon cancer cells. 109 The antiparasitic lipopeptide lead, hoshinoamide C 223 , was identified from Caldora penicillata . To determine the absolute configuration of the unusual amino acid moiety, 8-amino-4-methyloctanoic acid, found in 223 , two possible diastereomers of hoshinoamide C were synthesised.…”

Advances in Microbiome-Derived Solutions and Methodologies Are Founding a New Era in Skin Health and Care

“…Furthermore, multivariate analysis and machine learning tools have recently been implemented in GNPS to compare molecular profiles collected from different groups/types of samples [150]. Beyond its extensive application in natural product discovery, clinical and environmental studies, applications in skin studies included the identification of molecular signatures associated with individual lifestyles and further linked them to the built environment, investigating the impact of personal care products on the skin metabolomics and microbiome dynamics or even monitoring drugs and their metabolites directly on human skin [69,[151][152][153][154][155][156][157][158]. Molecular networking has also proven to efficiently assign the origin of molecules detected on human skin (skin cells, microbes, environment, and lifestyles) [147,156,159].…”

Marine Cyanobacteria as Sources of Lead Anticancer Compounds: A Review of Families of Metabolites with Cytotoxic, Antiproliferative, and Antineoplastic Effects

“…This effect was related to cell cycle arrest at the G2/M phase and the induction of apoptosis. However, the same cell cycle arrest or apoptosis pattern was not observed in normal human dermal fibroblasts (NHDF), suggesting a specificity to cancer cells [ 14 ]. Wenchangamide A has a structural resemblance to minnamide A ( Figure 15 b), a cyanobacterial natural product of Okeania hirsute .…”