DNA topoisomerase I inhibitors: cytotoxic flavones from Lethedon tannaensis.
From ethyl acetate and methanolic extracts of Lethedon tannaensis leaves, which were cytotoxic against murine leukemia (P-388) and human nasopharynx carcinoma (KB) cells, one new and six known 5-hydroxy-7-methoxyflavones variously substituted on the B ring were isolated and their structures determined by spectral analysis. Compounds active against KB cells were velutin (4) (IC50 4.8 microM), 7,3',5'-tri-O-methyltricetin (2) (IC50 22.2 microM), genkwanin (6) (IC50 30.6 microM), and the novel compound, 7,3',4'-tri-O-methyltricetin, named lethedocin (1) (IC50 47.6 microM). These flavones required the presence of hydroxyl groups at C-5 and C-4' and methoxyl groups at C-7 and C-3' for inhibition of calf thymus DNA topoisomerase I activity.
Zahir
A
A
Laboratoire de Chimie, URA 401 CNRS, Paris, France.
Jossang
A
A
Bodo
B
B
Provost
J
J
Cosson
J P
JP
Sévenet
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009510:New Caledonia; D010946:Plants, Medicinal / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D059004:Topoisomerase I Inhibitors