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. Four previously undescribed hirsutinolide-type sesquiterpenoids, along with twelve known analogues, were isolated from the aerial parts of Cyanthillium cinereum. Compound 1, a rarely occurring hirsutinolide-type sesquiterpenoid with 1,4-ether ring ruptured and containing a chlorine atom, exhibited significant anti-prostate cancer activity against PC-3 with IC50 values of 6.4 μM. [Display omitted] •Four previously undescribed hirsutinolides were discovered from Cyanthillium cinereum.•Compound 1 is a rarely occurring hirsutinolide with 1,4-ether ring ruptured.•The absolute configuration of 1 was determined by quantum chemical calculations of ECD spectra.•Compounds 1, 3, and 8–14 exhibited significant anti-prostate cancer activity.•Compound 1 exerted anti-proliferative effects by inducing apoptosis in PC-3 cells.