Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest

Bioassay‐guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc . (Vitaceae) led to the identification of one macrolide, lasiodiplodin ( 1 ), three sesquiterpenoids, 12‐hydroxy‐15‐oxoselina‐4,11‐diene ( 2 ), 1 β ,6 α ‐dihydroxyeudesm‐4(15)‐ene ( 3 ), and (7 R *)‐opposit‐4(15)‐ene‐1 β ,7‐diol ( 5 ), and a new diterpenoid, 16,18‐dihydroxykolavenic acid lactone ( 4 ). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC 50 values of 0.44 μ M (0.14 μg/ml) and 0.045 μg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance.