Laboratório de Produtos Naturais e Espectrometria de Massas (LaPNEM), Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição (FACFAN), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil.
Grupo de Estudos Biotecnologia e Bioprospecção Aplicados ao Metabolismo (GEBBAM), Universidade Federal da Grande Dourados (UFGD), Dourados, MS, Brazil.
Phytochem Anal. 2021 Nov;32(6):992-1002. doi: 10.1002/pca.3041. Epub 2021 Feb 25.
The chemical diversity of plants plays an essential role in the development of new drugs. However, new bioactive compound identification and isolation are challenging due to the complexity and time-consuming 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.
We aimed to determine bioactive compounds against resistant human melanoma cells from leaves of Aspidosperma subincanum, Copaifera langsdorffii, Coussarea hydrangeifolia, Guarea guidonea and Tapirira guianensis, using a metabolomics approach.
The extracts and fractions were obtained by accelerated solvent extraction (ASE) and tested against resistant melanoma cells SK-MEL-28 and SK-MEL-103. Chemical analysis was performed by high-performance diode array detector tandem mass spectrometry (HPLC-DAD-MS/MS). Chemical and biological data were analysed through univariate and multivariate analysis.
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 C. langsdorffii and T. guianensis 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 C. langsdorffii and T. guianensis, such as polyphenols and terpenes, were the main compounds correlated with the biological response.
These findings afford alternative pathways that are trustworthy and less time-consuming to identify new bioactive compounds against multidrug-resistant human melanoma cells.
植物的化学多样性在新药开发中起着至关重要的作用。然而，由于传统方法的复杂性和耗时性质，新的生物活性化合物的鉴定和分离具有挑战性。最近，替代策略变得流行起来，例如用统计学方法将化合物与生物活性相关联，从而克服生物活性天然产物研究中的瓶颈。
我们旨在使用代谢组学方法从 Aspidosperma subincanum、Copaifera langsdorffii、Coussarea hydrangeifolia、Guarea guidonea 和 Tapirira guianensis 的叶子中确定针对耐药性人类黑色素瘤细胞的生物活性化合物。
通过加速溶剂萃取（ASE）获得提取物和馏分，并对耐药性黑色素瘤细胞 SK-MEL-28 和 SK-MEL-103 进行测试。通过高效二极管阵列检测器串联质谱（HPLC-DAD-MS/MS）进行化学分析。通过单变量和多变量分析对化学和生物数据进行分析。
这些物种表现出高度的化学多样性，包括吲哚生物碱、糖基化类黄酮、没食子酰奎宁酸衍生物、肉桂酸衍生物和萜类化合物。ASE 分级分离根据物理化学性质分离化合物；只有 C. langsdorffii 和 T. guianensis 的提取物具有活性。化学图谱和生物测定的结果均采用代谢组学方法进行处理，以确定不同类别的次生代谢物对人类黑色素瘤细胞活力的贡献。分析表明，C. langsdorffii 和 T. guianensis 的代谢物，如多酚和萜类化合物，是与生物反应相关的主要化合物。
这些发现提供了替代途径，可以更可靠、更省时地鉴定针对多药耐药性人类黑色素瘤细胞的新生物活性化合物。
