Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells.

Polyporenic acids N-R ( 1 - 5 ), five novel 24-methylene lanostane triterpenes along with seven known polyporenic acids ( 6 - 12 ), were identified from the fruiting bodies of Buglossoporus quercinus . The isolation of compounds 1 - 12 was performed by a combination of multistep flash chromatography and reversed-phase high-performance liquid chromatography (HPLC). The structure determination was carried out by extensive spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) experiments. The isolated fungal metabolites were investigated for their antiproliferative activity in vitro by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the resistant Colo 320 human colon adenocarcinoma cell line expressing P-glycoprotein (ABCB1). The lanostane triterpenes exerted moderate antiproliferative activity with IC ₅₀ values in the range of 20.7-106.2 μM. A P-glycoprotein efflux pump modulatory test on resistant Colo 320 cells highlighted that fungal metabolites 3 , 5 , 8 , and 10 - 12 have the ability to inhibit the efflux pump activity of cancer cells. Moreover, the drug interactions of triterpenes with doxorubicin were studied by the checkerboard method. Compounds 3 - 4 , and 7 - 12 interacted in a synergistic manner, while an outstanding potency was detected for compound 9 , which was defined as strong synergism (CI = 0.276). The current study reveals that B. quercinus is a remarkable source of fungal steroids with considerable chemosensitizing activity on cancer cells.