Phenolic Compounds From Diarthron Lessertii: Isolation, Cytotoxicity, and Interaction With Cancer Signaling Pathway, Foxo3a Publisher



Biganeh H ; Sadeghi M ; Miroliaei M ; Khanavi M ; Ghanadian M
Source: Research in Pharmaceutical Sciences Published:2026

Abstract

Background and purpose: Natural products are valuable sources of anticancer agents. This study investigated the phytochemical composition of Diarthron lessertii shoot extract and evaluated the anticancer potential of its isolated phenolic constituents. Experimental approach: Phenolic compounds were isolated using chromatographic techniques and identified by one- and two-dimensional NMR spectroscopy and ESI-MS analysis. Cytotoxicity against HeLa cervical cancer cells was assessed using the MTT assay. A luciferase reporter assay evaluated the effect of the most active compound on FOXO3a was examined through molecular docking. Findings/Results: Nine phenolic compounds were isolated and characterized from D. lessertii, including two lignans (epinortrachelogenin and isolariciresinol), one biflavonoid (stelleranol), one bicoumarin (daphnoretin), and five flavonoids (genkwanin, apigenin 7,4'-dimethyl ether, naringenin, apigenin, and dihydrokaempferol). Among the isolated compounds, epinortrachelogenin (compound 1) showed the strongest cytotoxic activity against HeLa cells, with an IC 50 value of 80.37 ± 4.72 μM. In luciferase assays, compound 1 selectively activated FOXO3a, reaching 2274 relative luminescence units at 100 pM. Molecular docking further supported these findings, revealing favorable binding of compound 1 within the FOXO3a binding pocket. Conclusion and implications: Epinortrachelogenin exhibited notable cytotoxicity and selective FOXO3a activation, supported by docking analysis. These findings identify this lignan as a promising lead compound for the development of FOXO3a-targeted anticancer agents. © 2026 Research in Pharmaceutical Sciences.