Profiling and antiproliferative activity of tropical seaweed extracts using LC-HRMS and in silico approaches

Abstract

Seaweeds offer significant potential at the intersection of functional food development and drug discovery, as they can be safely incorporated into the human diet and exhibit antiproliferative activity against cancer cell lines. This study aims to investigate the metabolite profile of water extracts from seaweed and evaluate their antiproliferative properties. The methodology employed in this study encompassed six key steps: extraction, LC-HRMS-based metabolite identification, antiproliferative assays, correlation analysis using partial least squares regression (PLSR), molecular docking, and molecular dynamics (MD) simulations. Metabolites were extracted from three seaweed species via maceration using deionized water, followed by profiling through liquid chromatography–high-resolution mass spectrometry (LC-HRMS). Among the extracts, Sargassum cinereum demonstrated the most potent antiproliferative activity, with an IC₅₀ value of 46.89 μg/mL as determined by the MTT assay. PLSR analysis identified meconic acid as a key predictor of cell viability. In the in silico analysis, docking scores obtained from AutoDock Vina were re-ranked using the XGBoost machine learning algorithm. The top-ranked compounds based on binding affinity to the target protein (PDB ID: 7KP8) were (3β,22E,24S)-3-Hydroxyergosta-5,8,22-trien-7-one from Ulva lactuca (−10.02 kcal/mol), 2,3,5,6,8-pentahydroxy-1,4-naphthalenedione from S. cinereum (−8.40 kcal/mol), and 5,2′,5′-trihydroxy-3,7,8-trimethoxyflavone 2′-acetate from Turbinaria decurrens (−8.80 kcal/mol). Molecular dynamics simulations over 100 ns confirmed the stability of these ligand–protein complexes. These findings indicate that metabolites derived from U. lactuca, S. cinereum, and T. decurrens possess promising potential compounds with inhibitory activity against lung cancer progression.