Characterization of new pyrone-containing flavones from Helichrysum petiolare Hilliard & B.L. Burtt

• Comprehensive phytochemical analysis of Helichrysum petiolare , a South African medicinally important plant. • First characterization of two new pyrone-containing flavones from natural sources. • Dose-dependant cytotoxicity of phytochemicals from H. petiolare against the MDA-MB-231 and HeLa cell lines. Helichrysum petiolare Hilliard & B.L. Burtt. (Asteraceae), native to the Cape Floral Region of South Africa, is traditionally used in the management of wounds, respiratory complaints, and diabetes. Although extensive studies on its extracts, few have focused on the bioactivity of the individual phytochemicals. In this study, chromatographic processing of the H. petiolare leaf total extract led to the isolation and identification of ten compounds C1–C10 ) using NMR, FTIR, and HRESIMS spectroscopy. Two pyrone-containing flavones ( C1 and C2 ) are reported for the first time from natural sources. The known compounds identified included flavonoids ( C3–C5 ), phenolics ( C6–C9 ), and a sterol ( C10 ). The MTT assay revealed dose-dependent cytotoxicity of C1–C4 only against MDA-MB-231 (breast cancer), HeLa (cervical cancer), and HEK-293 (non-cancerous kidney) cell lines after 24 h exposure. Notably, C4 demonstrated selective activity toward HeLa cells (45 % viability reduction at 100 µM; IC₅₀ = 89.19 µg/mL). This is the first report of compounds C1–C10 from H. petiolare and their in vitro cytotoxic profile. Despite moderate activity, this work provides a foundation for further pharmacological investigations of derivatives of these metabolites in cancer management.