Ghini Veronica, Tristán Ana Isabel, Di Paco Giorgio, Massai Lara, Mannelli Michele, Gamberi Tania, Fernández Ignacio, Rosato Antonio, Turano Paola, Messori Luigi
Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino 50019, Italy.
Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Ctra. Sacramento, s/n, Almeria 04120, Spain.
J Proteome Res. 2025 Feb 7;24(2):813-823. doi: 10.1021/acs.jproteome.4c00904. Epub 2025 Jan 6.
A combination of pathway enrichment and metabolite clustering analysis is used to interpret untargeted H NMR metabolomics data, enabling a biochemically informative comparison of the effects induced by a panel of known cytotoxic gold(I) and gold(III) compounds in A2780 ovarian cancer cells. The identification of the most dysregulated pathways for the major classes of compounds highlights specific chemical features that lead to common biological effects. The proposed approach may have broader applicability to the screening of metal-based drug candidate libraries, which is always complicated by their multitarget nature, and support the comprehensive interpretation of their metabolic actions.
采用通路富集和代谢物聚类分析相结合的方法来解释非靶向氢核磁共振代谢组学数据，从而能够对一组已知的细胞毒性金（I）和金（III）化合物在A2780卵巢癌细胞中诱导的效应进行具有生物化学信息的比较。对主要类别化合物中失调最严重的通路进行鉴定，突出了导致共同生物学效应的特定化学特征。所提出的方法可能在基于金属的药物候选库筛选中具有更广泛的适用性，这类筛选总是因其多靶点性质而变得复杂，该方法还支持对其代谢作用进行全面解释。
