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,18 S,19R)-diacetoxy- 18,19-epoxy-6-hydroxy-2-(2-me thylbutanoyloxy)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 IC50 values below 3 muM, while compounds 2 , 6, 8, and 9 were less effective