Phenolic compounds from Diarthron lessertii: isolation, cytotoxicity, and interaction with cancer signaling pathway, FOXO3a

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 IC50 value of 80.37 +/- 4.72 mu M. 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.