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

Abstract

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.

Autoren

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 AA Ibrahim
Khaled A Shams
Nahla S Abdel-Azim
Christopher J Kampf
Thomas Efferth
Paul W Paré
Mohamed-Elamir F Hegazy

DOI

10.3390/molecules28020674

eISSN

1420-3049

Ausgabe der Veröffentlichung

2

Zeitschrift

Molecules

Sprache

en

Online publication date

2023

Paginierung

674 - 674

Status

Published online

Herausgeber

MDPI AG

Herausgeber URL

http://dx.doi.org/10.3390/molecules28020674

Datum der Datenerfassung

2023

Titel

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

Ausgabe der Zeitschrift

28

Data source: Crossref

Abstract

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.

Addresses

Phytochemistry Laboratory, National Organization for Drug Control and Research, Giza 12622, Egypt.

Autoren

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 AA Ibrahim
Khaled A Shams
Nahla S Abdel-Azim
Christopher J Kampf
Thomas Efferth
Paul W Paré
Mohamed-Elamir F Hegazy

DOI

10.3390/molecules28020674

eISSN

1420-3049

Externe Identifier

PubMed Identifier: 36677732
PubMed Central ID: PMC9862008

Open access

true

ISSN

1420-3049

Ausgabe der Veröffentlichung

2

Zeitschrift

Molecules (Basel, Switzerland)

Schlüsselwörter

Centaurea
Sesquiterpenes
Lactones
Plant Extracts
Antineoplastic Agents
Chromatography, Liquid
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Egypt
Tandem Mass Spectrometry
Phytochemicals

Sprache

eng

Medium

Electronic

Online publication date

2023

Open access status

Open Access

Paginierung

674

Datum der Veröffentlichung

2023

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2023

Titel

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

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

28

Files

https://www.mdpi.com/1420-3049/28/2/674/pdf?version=1673346700 https://europepmc.org/articles/PMC9862008?pdf=render

Data source: Europe PubMed Central

Abstract

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.

Date of acceptance

2023

Autoren

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 AA Ibrahim
Khaled A Shams
Nahla S Abdel-Azim
Christopher J Kampf
Thomas Efferth
Paul W Paré
Mohamed-Elamir F Hegazy

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/36677732

DOI

10.3390/molecules28020674

eISSN

1420-3049

Externe Identifier

PubMed Central ID: PMC9862008

Ausgabe der Veröffentlichung

2

Zeitschrift

Molecules

Schlüsselwörter

Centaurea
LC-MS/MS
cytotoxicity
molecular networking
sesquiterpene lactones
Plant Extracts
Chromatography, Liquid
Drug Resistance, Multiple
Egypt
Drug Resistance, Neoplasm
Tandem Mass Spectrometry
Antineoplastic Agents
Centaurea
Phytochemicals
Sesquiterpenes
Lactones

Sprache

eng

Country

Switzerland

PII

molecules28020674

Datum der Veröffentlichung

2023

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2023

Titel

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

Sub types

Journal Article

Ausgabe der Zeitschrift

28

Data source: PubMed

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

Files

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