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Proline Analogue of Nitrosourea as a New Cytotoxic Prodrug
Author(s) -
StankiewiczKranc Anna,
Bielawska Anna,
Bielawski Krzysztof,
Skrzydlewska Elzbieta
Publication year - 2009
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900120
Subject(s) - carmustine , chemistry , prodrug , nitrosourea , proline , glutathione reductase , antioxidant , superoxide dismutase , glutathione , biochemistry , glutathione peroxidase , oxidative stress , hydrogen peroxide , enzyme , pharmacology , amino acid , chemotherapy , cyclophosphamide , biology , genetics
Carmustine is frequently used as anticancer drug. High toxicity and low selectivity reduces the application of this drug. Though, there is a necessity to find new compounds characterized by similar therapeutic effects but a higher selectivity and safety. As a result, the proline analogue of nitrosourea, N ‐[ N ′‐(2‐bromophenyl)‐ N ′‐nitrosocarbamoyl]proline ( AC ), has been synthesized. The aim of this study was to compare the influence of carmustine and the proline analogue of nitrosourea on the antioxidant abilities of fibroblasts and leukemia cells, MOLT4. It was shown that carmustine as well as AC cause an increase in hydrogen peroxide concentration in normal and neoplastic cells. Incubation with both compounds led to a diminution of the activity of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and reductase. Changes in activity / level of antioxidant parameters were accompanied by augmentation of lipid and oxidative protein modifications. In conclusion, carmustine and AC cause changes in the antioxidative system of normal and MOLT4 cells and are a reason of oxidative stress formation.