Hirsutinolide-type sesquiterpenoids with anti-prostate cancer activity from Cyanthillium cinereum

Four previously undescribed hirsutinolide-type sesquiterpenoids, cyanolides A-D (1-4), along with twelve known analogues (5-16), were isolated from the aerial parts of Cyanthillium cinereum. Their structures were determined by comprehensive analysis of NMR, HRESIMS, and ECD spectra. Compound 1 is a rarely occurring hirsutinolidetype sesquiterpenoid with 1,4-ether ring ruptured and containing a chlorine atom, and compounds 13-16 were reported from this plant for the first time. All compounds were tested for their inhibiting effects on prostate cancer cells. As a result, compounds 1, 3, and 8-14 exhibited significant anti-prostate cancer activity against PC3 and LNCaP cells with IC50 values ranging from 2.2 +/- 0.4 to 8.5 +/- 0.7 mu M and 3.0 +/- 0.7 to 10.5 +/- 1.1 mu M, respectively. The preliminary structure-activity relationship was discussed. Further investigation showed that compound 1 induced apoptosis in PC-3 cells.