Structurally diverse sesquiterpenoids with anti-MDR cancer activity from Penicillium roqueforti

Five new rare nor-eremophilane-type sesquiterpenoids, peniroqueforins E–H and J (1–4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), together with four known compounds (6 and 10–12), were isolated and identified from fungus Penicillium roqueforti. Their structures and absolute configurations were elucidated by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. These compounds were evaluated for the anti-MDR (multi-drug resistance) cancer activity by SW620/Ad300 cells. The IC₅₀ value of PTX (paclitaxel) with 1 in SW620/Ad300 cells was 50.36 nM, which was 65-fold stronger than PTX (IC₅₀ = 3.26 μM). Further molecular docking research disclosed the affinity between compound 1 and P-gp (P-glycoprotein), which highlighted the nor-eremophilane-type sesquiterpenoid (1) as a potential lead for MDR reversal in cancer cells via inhibiting P-gp.