Screening of Triterpenoids Isolated from Phyllanthus flexuosus for DNA Topoisomerase Inhibitory Activity
Abstract
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-3β,15α-diol (1), olean-12-en-3β,15α,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo II activity with IC50 values in the range of 10−39 μM.
*
To whom correspondence should be addressed. Fax: (+81)726-90-1005. E-mail: [email protected].
†
Osaka University of Pharmaceutical Sciences.
‡
Graduate School of Pharmaceutical Sciences, Kyoto University.
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