Antiproliferative Compounds from Cleistanthus boivinianus from the Madagascar Dry Forest

The two new lignans 3 alpha-O-(beta-D-glucopyranosyl)desoxypodophyllotoxin) (1) and 4-O-(beta-D-glucopyranosyl)dehydropodophyllotoxin (2) were isolated from Cleistanthus boivinianus, together with the known lignans deoxypicropodophyllotoxin (3), (+/-)-beta-apopicropodophyllin (4), (-)-desoxypodophyllotoxin (5), (-)-yatein (6), and beta-peltatin-5-O-beta-D-glucopyranoside (7). The structures of all compounds were characterized by spectroscopic techniques. Compounds 1, 4, and 5 showed potent antiproliferative activities against the A2780 ovarian cancer cell line, with IC50 values of 33.0 +/- 3.6, 63.1 +/- 6.7, and 230 +/- 1 nM, respectively. Compounds 2 and 7 showed only modest A2780 activities, with IC50 values of 2.1 +/- 0.3 and 4.9 +/- 0.1 mu M, respectively, while compounds 3 and 6 had IC50 values of >10 mu M. Compound 1 also had potent antiproliferative activity against the HCT-116 human colon carcinoma cell line, with an IC50 value of 20.5 nM, and compound 4 exhibited modest antiproliferative activity against the A2058 human caucasian metastatic melanoma and MES-SA human uterine sarcoma cell lines, with IC50 values of 4.6 and 4.0 mu M, respectively.