New cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia membranacea.

Bioassay-guided fractionation of an EtOAc-soluble extract of Casearia membranacea has resulted in the isolation of six new clerodane diterpenes, caseamembrins A-F (1-6), and a known compound, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (7). The structures of 1-6 were established on the basis of extensive 1D and 2D NMR spectroscopic analysis. In addition, the new derivatives, 8 and 9, were prepared by acylation of 7 and 3, respectively. The isolated diterpenoids and their derivatives were tested against human prostate (PC-3) and hepatoma (Hep3B) cancer cells. Compounds 1, 3-5, and 7 exhibited cytotoxicity against both tumor cells, with IC(50) values below 3 micromicro, while compounds 2, 6, 8, and 9 were less effective.