Isoprenylated phenolic derivatives from Corethrodendron scoparium and their anti-triple negative breast cancer...

Seventeen undescribed isoprenylated phenolics, including depsidones (1 and 2), depsides (3 and 4), stilbenoid (5), isoflavonoids (6-12), and flavonoids (13-17), together with thirteen known analogues (18-30), were isolated from the roots and stems of Corethrodendron scoparium (Fabaceae). Structurally, compounds 1 and 2 possess an unprecedented isoprenylated depsidone framework, while compound 6 represents an unusual subtype of rearranged isoprenylated isoflavone. Their structures were established by spectroscopic methods and chiral analysis. Furthermore, a plausible biosynthetic pathway for 1, 2, and 6 was proposed. The anti-triple negative breast cancer (anti-TNBC) potential of these isolates was systematically evaluated. Compounds 8, 13, and 15 emerged as potent cytotoxic agents against MDA-MB-231 and MDA-MB-468 cells, with IC₅₀ values ranging from 2.5 to 3.95 μM. Preliminary mechanistic studies revealed that compound 15 inhibited cell proliferation by inducing G1 phase arrest in both TNBC cell lines. To assess selectivity, cytotoxicity against the non-cancerous HEK-293T cell line was also measured. Impressively, hedysarimcoumestan D (24) exhibited an excellent safety profile, with a selectivity index (SI = 13.29) that outperformed the clinical drug paclitaxel.