Reduction of daunorubicin in the presence of sulfur-containing peptides |
| |
Authors: | Chantal Houe-Levin Kouider Benzineb Monique Gards-Albert Zohreh Abedinzadeh Christiane Ferradini |
| |
Institution: | Laboratoire de Chimie Physique, URA 400, Université Paris V, 45 rue des Saints-Pères, 75 270, Paris Cedex 06, France |
| |
Abstract: | Daunorubicin, an anthracycline antitumor antibiotic, was reduced in the presence of reduced (GSH) or oxidized (GSSG) glutathione to evaluate the possibilities of detoxification or of potentiation of the drug by these compounds. The reductants were .COO? free radicals produced by γ radiolysis. In both cases, the final product is 7-deoxydaunomycinone, i.e., the same as without glutathione. The reduction yield is also the same as without GSH or GSSG (0.23 μmol·J?1). No glutathione depletion was observed. Limits for the rate constants of some possible nonenzymatic detoxification reactions are given. To evaluate the possible interactions of daunorubicin with sulfur-containing proteins, the reduction of this drug by .COO? free radicals was also studied in the presence of a polypeptide containing two disulfide bridge are, respectively, 0.23 μmol·J?1 7-deoxydaunomycinone. The yields of reduction of the drug and of a protein disulfide bridge are, respectively, 0.23 μmol·J?1 and ≤ 6 nmol·J?1. These values indicate thet disulfide radical anions of the protein can reduce the drug, giving back the disulfide bridge, but that the drug transients niether oxidize nor reduce the protein. |
| |
Keywords: | Daunorubicin γ Radiolysis Reduced glutathione Oxidized glutathione Drug-glutathione interations Free radicals |
本文献已被 ScienceDirect 等数据库收录! |
|