Feature-Based Molecular Networking for the Exploration of the Metabolome Diversity of Common Egyptian Species in Relation to Their Cytotoxic Activity.

is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian species, was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of and compare it to other members of the genus in pursuance of identifying its bioactive principles. An LC-MS/MS analysis approach synchronized with feature-based molecular networks was adopted to offer a holistic overview of the metabolome diversity of the Egyptian species. The studied plants included and . Their constitutive metabolome showed diverse chemical classes such as cinnamic acids, sesquiterpene lactones, flavonoids, and lignans. Linking the recorded metabolome to the previously reported cytotoxicity identified sesquiterpene lactones as the major contributors to this activity. To confirm our findings, bioassay-guided fractionation of was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC of 1.817 µM against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.