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 IC₅₀ 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.