Relationship of the reductive metabolism of indicine N-oxide to its antitumor activity.

Res Commun Chem Pathol Pharmacol 1979 Jun; 24(3):559-69.RC

Several pyrrolizidine alkaloids have been demonstrated to have antitumor activity in experimental tumor systems. In general the free base form of the alkaloid exhibits greater biological activity than the corresponding N-oxide and the N-oxide must be metabolized to the base for the subsequent formation of alkylating intermediates. Indicine N-oxide is an exception in that it is a more active antitumor agent than its free base indicine. Studies of the antitumor activity and metabolism of indicine N-oxide, and the closely related compound, heliotrine N-oxide, given orally and intraperitoneally to mice bearing P-388 leukemia, suggest that conversion of indicine N-oxide to indicine is not essential for its antitumor activity.