Feature-Based Molecular Networking for the Exploration of the Metabolome Diversity of Common Egyptian <i>Centaurea</i> Species in Relation to Their Cytotoxic Activity
Eman H. Reda,
Nesrine M. Hegazi,
Mona Marzouk,
Zienab T. Abdel Shakour,
Ali M. El-Halawany,
El-Sayeda A. El-Kashoury,
Tarik A. Mohamed,
Mahmoud A. A. Ibrahim,
Khaled A. Shams,
Nahla S. Abdel-Azim,
Christopher J. Kampf,
Thomas Efferth,
Paul. W. Paré,
Mohamed-Elamir F. Hegazy
Affiliations
Eman H. Reda
Phytochemistry Laboratory, National Organization for Drug Control and Research, Giza 12622, Egypt
Nesrine M. Hegazi
Phytochemistry and Plant Systematics Department, National Research Centre, Dokki, Cairo 12622, Egypt
Mona Marzouk
Phytochemistry and Plant Systematics Department, National Research Centre, Dokki, Cairo 12622, Egypt
Zienab T. Abdel Shakour
Phytochemistry Laboratory, National Organization for Drug Control and Research, Giza 12622, Egypt
Ali M. El-Halawany
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
El-Sayeda A. El-Kashoury
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
Tarik A. Mohamed
Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt
Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt
Nahla S. Abdel-Azim
Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt
Christopher J. Kampf
Department for Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
Thomas Efferth
Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences Chemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany
Paul. W. Paré
Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX 79409, USA
Mohamed-Elamir F. Hegazy
Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt
Centaurea is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian Centaurea species, C. lipii was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of C. lipii 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 Centaurea species. The studied plants included C. alexandrina, C. calcitrapa, C. eryngioides, C. glomerata, C. lipii, C. pallescens, C. pumilio, and C. scoparia. 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 C. lipii was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC50 of 1.817 µM against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of C. lipii and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.
