Discovery of myrsinane diterpenoids from Euphorbia monostyla with cytotoxic potential.

A phytochemical investigation of the aerial parts of Euphorbia monostyla Prokh., an endemic species of Turkmenistan, led to the isolation of twelve previously undescribed myrsinane-type diterpenoids, euphomonophanes F-Q (1-12). Their structures were elucidated through comprehensive spectroscopic analyses, including 1D, 2D NMR, and HRESIMS. Relative configurations were established by NOESY correlations, while absolute configurations were determined by a combination of ECD calculations and single-crystal X-ray diffraction analysis. All compounds were evaluated for their cytotoxicity against HeLa (human cervical carcinoma), HCT-8 (human ileocecal adenocarcinoma), and MCF-7 (human breast cancer) cell lines using the MTT assay with doxorubicin and docetaxel as positive controls, followed by preliminary structure-activity relationship analysis. Among them, euphomonophane F (1) and K (6) exhibited the strongest cytotoxicity against HeLa cells with IC50 values of 15.37 ± 0.52 and 26.86 ± 1.86 μM, respectively, while euphomonophanes H (3) and L (7) showed activity with IC50 values of 43.10 ± 2.41 and 37.23 ± 2.21 μM, respectively. Euphomonophane H (3) also demonstrated activity against MCF-7 and HCT-8 cells with IC50 values of 24.66 ± 1.25 and 30.76 ± 2.03 μM. These findings highlight the potential of the myrsinane scaffold as a valuable framework for further structural optimization and investigation toward anticancer agents.