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However, new bioactive compound identification and isolation are challenging due to the complexity and time\u2010consuming nature of the traditional process. Recently, alternative strategies have become popular, such as the statistical approach to correlate compounds with biological activities, overcoming bottlenecks in bioactive natural product research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to determine bioactive compounds against resistant human melanoma cells from leaves of <jats:italic>Aspidosperma subincanum<\/jats:italic>, <jats:styled-content style=\"fixed-case\"><jats:italic>Copaifera langsdorffii<\/jats:italic><\/jats:styled-content>, <jats:italic>Coussarea hydrangeifolia<\/jats:italic>, <jats:italic>Guarea guidonea<\/jats:italic> and <jats:italic>Tapirira guianensis<\/jats:italic>, using a metabolomics approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>The extracts and fractions were obtained by accelerated solvent extraction (ASE) and tested against resistant melanoma cells SK\u2010MEL\u201028 and SK\u2010MEL\u2010103. Chemical analysis was performed by high\u2010performance diode array detector tandem mass spectrometry (HPLC\u2010DAD\u2010MS\/MS). Chemical and biological data were analysed through univariate and multivariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The species present high chemical diversity, including indole alkaloids, glycosylated flavonoids, galloylquinic acid derivatives, cinnamic acid derivatives, and terpenes. The ASE fractionation separated the compounds according to the physicochemical properties; only <jats:styled-content style=\"fixed-case\"><jats:italic>C. langsdorffii<\/jats:italic><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>T. guianensis<\/jats:italic><\/jats:styled-content> extracts were active. Both results from the chemical profile and the biological assay were treated using a metabolomics approach to identify the contribution of different classes of secondary metabolites in the viability of human melanoma cells. The analyses showed the metabolites from <jats:styled-content style=\"fixed-case\"><jats:italic>C. langsdorffii<\/jats:italic><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>T. guianensis<\/jats:italic><\/jats:styled-content>, such as polyphenols and terpenes, were the main compounds correlated with the biological response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings afford alternative pathways that are trustworthy and less time\u2010consuming to identify new bioactive compounds against multidrug\u2010resistant human melanoma cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pca.3041","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:34:20Z","timestamp":1614299660000},"page":"992-1002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Application of the metabolomics approach to the discovery of active 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