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

Abstract

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.

• Authors: G Powis, M M Ames, J S Kovach
• Journal: Research communications in chemical pathology and pharmacology (Res Commun Chem Pathol Pharmacol) Vol. 24 Issue 3 Pg. 559-69 (Jun 1979) ISSN: 0034-5164 [Print] United States
• PMID: 451340 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Cyclic N-Oxides
• Pyrrolizidine Alkaloids
• heliotrine N-oxide

Topics

• Anaerobiosis
• Animals
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Cyclic N-Oxides (metabolism, pharmacology, therapeutic use)
• In Vitro Techniques
• Leukemia, Experimental (drug therapy, metabolism)
• Male
• Mice
• Microsomes, Liver (metabolism)
• Oxidation-Reduction
• Pyrrolizidine Alkaloids (metabolism, pharmacology, therapeutic use)