Proline Analogue of Nitrosourea as a New Cytotoxic Prodrug

Abstract

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.

Synthesis of the Bifunctional Ligand N,Nʹ-[1,4- Phenylenebis(iminocarbonyl)]di(L-phenylalanine) and Crystal Structure of Its Supramolecular Coordination Polymer with Lead(II)

“…1), was synthesized by addition of L-phenylalanine to p-phenylene diisocyanate following a related literature procedure [46]. The com- …”

Uso de carmustina associada a nanoemulsões ricas em colesterol (LDE) para tratamento da aterosclerose induzida em coelhos

“…A administração sistêmica prolongada está associada a severos efeitos colaterais como mielossupressão, toxicidade hepática e hematológica (Seong et al, 2003;Stankiewicz-Kranc et al, 2009;Kuo & Liang, 2011). Essas reações adversas ocorrem pela inespecificidade do fármaco pelas células alvo, a qual pode ser revertida a partir da ligação de agentes farmacológicos a transportadores, aumentando sua especificidade.…”