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 hirsutinolide-type 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 PC-3 and LNCaP cells with IC 50 values ranging from 2.2 ± 0.4 to 8.5 ± 0.7 μM and 3.0 ± 0.7 to 10.5 ± 1.1 μM, respectively. The preliminary structure-activity relationship was discussed. Further investigation showed that compound 1 induced apoptosis in PC-3 cells.