What question did this study set out to answer?

The aim is to explore Moringa oleifera pericarp as a source of anticancer agents and identify potent compounds.

July 6, 2026Scientific Reports0 citationsOpen Access

Valorization of Moringa oleifera pericarp via semi-synthetic sugar-based enone derivatives with anticancer potential: phytochemical isolation, cytotoxic evaluation, and dual EGFR/CAIX targeting

MMMayye MajedMansoura University AGAmal A. GalalaDamietta University DODina I.A. OthmanMansoura University

Key Points

The aim is to explore Moringa oleifera pericarp as a source of anticancer agents and identify potent compounds.
Bioassay-guided fractionation of Moringa oleifera pericarp extract to identify active fractions.
Semi-synthetic modification of major compound M2 to create derivatives S1 M2 and S2 M2.
Evaluation of cytotoxic activity against HepG2 and HCT116 cancer cell lines and selectivity in WI-38 fibroblasts.
S2 M2 showed IC50 values of 5.97 ± 0.19 µM against HepG2 and 11.52 ± 0.37 µM against HCT116 cells.
S2 M2 exhibited strong EGFR-TK inhibition with IC50 of 0.40 ± 0.008 µM and CAIX inhibition with IC50 of 0.27 ± 0.01 µM.
Molecular docking confirmed stable binding of S2 M2 to EGFR-TK and CAIX active sites.

Abstract

Abstract Moringa oleifera pericarp, an underutilized agro-waste, was investigated as a potential source of anticancer agents. In this study, bioassay-guided fractionation of the pericarp extract led to the identification of the ethyl acetate fraction as the most active fraction, showing notable antioxidant, antimicrobial, and cytotoxic activities. Subsequent purification afforded three compounds: 4-( α -L-rhamnopyranosyloxy)-benzaldehyde ( M 1 ), 4-( α -L-rhamnopyranosyl) benzyl alcohol ( M 2 ), and 4-(hydroxymethyl) phenol-1- O - β -D-glucopyranosyl-(1''→3')- O - α -L-rhamnopyranoside ( M 3 ). The major constituent, M 2 , was semi-synthetically modified by Steglich esterification with cinnamic acid and crotonic acid to yield two sugar-based enone derivatives, S1 M2 and S2 M2 . Structural elucidation was performed using IR, MS, and NMR spectroscopy. The cytotoxic activity of the isolated and semi-synthesized compounds was evaluated against HepG2 and HCT116 cancer cell lines, and selectivity was assessed using normal WI-38 fibroblasts. Among the tested compounds, S2 M2 exhibited the most potent cytotoxicity, with IC 50 values of 5.97 ± 0.19 µM and 11.52 ± 0.37 µM against HepG2 and HCT116 cells, respectively, together with favorable selectivity. In addition, S2 M2 showed strong inhibitory activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK) and carbonic anhydrase IX (CAIX), with IC 50 values of 0.40 ± 0.008 µM and 0.27 ± 0.01 µM, respectively. Molecular docking and 100-ns molecular dynamics simulations supported the stable binding of S2 M2 within the active sites of EGFR-TK and CAIX, and MM-GBSA calculations confirmed its favorable binding free energy. Structure–activity relationship analysis suggested that the α , β -unsaturated carbonyl moiety significantly contributed to the observed anticancer activity. These findings highlight M. oleifera pericarp as a promising source of bioactive glycosylated phenolic scaffolds and identify S2 M2 as a potential dual-target anticancer lead for further development.

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