Table of Contents
Metal-Based Drugs
Volume 1, Issue 2-3, Pages 183-193
http://dx.doi.org/10.1155/MBD.1994.183

Degradation of Anthracycline Antitumor Compounds Catalysed by Metal Ions

Laboratoire de Chimie Bioinorganique, LPCB (URA CNRS 198), Université de Paris Nord, 74 rue Marcel Cachin, Bobigny F - 93012, France

Received 7 September 1993

Copyright © 1994 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The influence of some metal ions on the degradation of anthracyclines was examined. One of the degradation products is the 7,8-dehydro-9,10-desacetyldoxorubicinone, D* (¥), usually formed by hydrolysis at slightly basic pH. D* is a lipophilic compound with no cytostatic properties. Its formation could be responsible for the lack of antitumor activity of the parent compound. The coordination of metal ions to anthracycline derivatives is required to have degradation products. Cations such as Na+, K+, or Ca2+ do not induce the D* formation however metals which can form stable complexes with doxorubicin afford D*. Iron(III) and copper(II) form appreciable amount of D* at slightly acidic pH. Terbium(III) forms D* but its complex is stable only at slightly basic pH. Palladium(II) which does not form D*. The influence of the coordination mode of metal ions to anthracycline on the D* formation is discussed.