DNA TOPOISOMERASE-I INHIBITORS - CYTOTOXIC FLAVONES FROM LETHEDON TANNAENSIS

From ethyl acetate and methanolic extracts of Lethedon tannaensis leav es, which were cytotoxic against murine leukemia (P-388) and human nas opharynx carcinoma (KB) cells, one new and six known 5-hydroxy-7-metho xyflavones 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 mu M), 7,3',5'-tri-O-methyltriceti n (2) (IC50 22.2 mu M), genkwanin (6) (IC50 30.6 mu M), and the novel compound, 7,3',4'-tri-O-methyltricetin, named lethedocin (1) (IC50 47. 6 mu M). 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.