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 μM), 7,3‘,5‘-tri-O-methyltricetin (2) (IC50 22.2 μM), genkwanin (6) (IC50 30.6 μM), and the novel compound, 7,3‘,4‘-tri-O-methyltricetin, named lethedocin (1) (IC50 47.6 μM). 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.