Cytotoxic Polyhydroxylated Oleanane Triterpenoids from Cissampelos pareira var. hirsuta

Three new polyhydroxylated oleanane triterpenoids, cissatriterpenoid A−C (1−3), along with one known analogue (4), were isolated from the whole plant of Cissampelos pareira var. hirsuta. Their chemical structures were elucidated by extensive spectroscopic data (IR, HR-ESI-MS, (1)H-NMR, (13)C-NMR, DEPT, (1)H-(1)H COSY, HSQC, HMBC, NOESY) and the microhydrolysis method. The isolation of compounds 1–4 represents the first report of polyhydroxylated oleanane triterpenoids from the family Menispermaceae. All isolated compounds were evaluated for their cytotoxicity against five human cancer cell lines, and the inhibitory activity against NO release in LPS-induced RAW 264.7 cells. Compound 3 showed the most potent cytotoxic activities against the A549, SMMC-7721, MCF-7, and SW480 cell lines, with IC(50) values of 17.55, 34.74, 19.77, and 30.39 μM, respectively, whereas three remaining ones were found to be inactive. The preliminary structure–activity relationship analysis indicated that the γ-lactone ring at C-22 and C-29, and the olefinic bond at C-12 and C-13 were structurally required for the cytotoxicity of polyhydroxylated oleanane triterpenoids against these four cell lines. Based on lipid-water partition coefficients, compound 3 is less lipophilic than 1 and 4, which agrees with their cytotoxic activities. This confirms the potential of C. pareira var. hirsuta in the tumor treatment.