Screening of triterpenoids isolated from Phyllanthus flexuosus for DNA topoisomerase inhibitory activity

DNA topoisomerases (Topos) are enzymes that play a crucial role in DNA metabolism events such as replication, transcription, recombination, and chromosome segregation at mitosis. Thus, Topo inhibitors could be expected to have antitumor effects. Naturally occurring lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus were screened for human Topos I and II inhibitory activities. Olean-12-en-3beta,15alpha-diol (1), olean-12-en-3beta,15alpha,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo 11 activity with IC50 values in the range of 10-39 muM.