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-3 beta,15 alpha-diol (1), olean-12-en-3 beta,15 alpha,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo II activity with IC(50) values in the range of 10-39 microM.
Wada
S
S
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. wada@oysun01.oups.ac.jp
Iida
A
A
Tanaka
R
R
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D029803:Phyllanthus / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D010957:Plasmids; D013237:Stereoisomerism; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000094062:Betulinic Acid; D000094042:Lupanes
D000972:Antineoplastic Agents, Phytogenic; D004247:DNA; D004791:Enzyme Inhibitors; D005047:Etoposide; D009828:Oleanolic Acid; D053978:Pentacyclic Triterpenes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes; C446315:olean-12-en-3,15,24-triol; C446313:olean-12-en-3,15-diol; C446314:olean-12-en-3,24-diol; C002503:betulin; D000094062:Betulinic Acid; C010480:lupeol; D000094042:Lupanes