Antitumor agents. 125. New 4 beta-benzoylamino derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin and 4 beta-benzoyl derivatives of 4'-O-demethylpodophyllotoxin as potent inhibitors of human DNA topoisomerase II.

A series of 4 beta-benzoylamino (5-17) derivatives of 4'-O-dimethyl-4- desoxypodophyllotoxin and 4 beta-benzoyl (18-20) derivatives of 4'-O-demethyl podophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 5-13 and 15-17 are more potent than etoposide in causing DNA breakage, while compounds 9, 10, 13, 14, 16, and 20 are more active than etoposide in their inhibition of the human DNA topoisomerase II. The order for the enzyme inhibitory activity of the derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin is 4 beta-arylamino > 4 beta-benzylamino > 4 beta-benzoylamino.