Identification of meroterpenoids from Bipolaris victoriae S27 and their potential activity against tumor metastasis and inhibition of the NF-κB signaling pathway

Three undescribed meroterpenoids, named bipolacochlioquinones A-C, together with seven known compounds, were isolated from the plant endophytic fungus Bipolaris victoriae S27 derived from the fresh stems of Rubia podantha Diels. Their structures were mainly determined by extensive spectroscopic analysis. The relative configurations of bipolacochlioquinones A-C were assigned using the ROESY spectrum, comparison of their spectral data with that reported in the literatures, and NMR calculations. Moreover, their complete absolute configurations were further established by electronic circular dichroism calculations using density functional theory. Among them, bipolacochlioquinone A is found to represent the first example of previously undescribed 6/6/6/6/6 pentacyclic dioxane-containing cochlioquinones, and bipolacochlioquinone B possesses a rare 6/6/6/6/5 pentacyclic system bearing a tetrahydrofuran ring fused to a polyketide and a sesquiterpenoid subunit. All compounds were evaluated for their inhibitory effects on tumor growth, metastasis, and the NF-κB signaling pathway. Among them, bipolacochlioquinone C and cochlioquinone A show the most potent cytotoxicities and NF-κB inhibitory activities. The effects of bipolacochlioquinone C and cochlioquinone A on the expression of NF-κB-associated proteins were also evaluated using western blotting. These results indicate that bipolacochlioquinone C and cochlioquinone A can inhibit the growth and metastasis of HCT116 and MDA-MB-231 cells by suppressing the NF-κB signaling pathway.