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Introduction. Early malignant tumor detection programs have significantly increased the survival rate of breast cancer patients but the results of drug therapy for this pathology are not always highly effective. Recently discovered iron-dependent cell death, ferroptosis, makes it a promising therapeutic target to reduce the recurrence rates.Objective – to study the induction of ferroptosis in breast cancer cells MCF-7 by quinazoline derivatives synthesized at the Research Institute of Experimental Diagnostics and Therapy of Tumors of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia and to evaluate its antitumor activity on transplanted breast carcinoma Ca-755.Materials and methods. Derivatives of 3-hydroxyquinazoline were obtained by chemical synthesis and have a purity of at least 95 %. In this study 2D cultivation of MCF7 cells, phase-contrast and fluorescence microscopy, and a model of experimental growth of breast carcinoma Ca-755 in female hybrids of immunocompetent mice F1 (C57Bl/6 × DBA/2) were used.Results. Five derivatives of 3-hydroxyquinazoline, analogues of erastine, were studied in this work. The ferroptotic cell death was identified by the level of lipid peroxidation at the concentrations of 1/3 and 1/5 IC50. The level of lipid peroxidation induced by compound 3 was comparable with the activity of erastin in MCF7 cells at both 1/3 and 1/5 of IC50, the activity of the other four quinazoline derivatives was 50–70 % of the activity of erastin. In in vivo experiments at a dose of 30 mg/kg the antitumor efficacy of the compound 3 was higher than that of erastin at the same dose.Conclusion. The data obtained suggest that quinazoline derivative 3 might be considered as a promissisng antitumor agent to treat breast cancer.

The dynamics of the production of nitric oxide (NO) metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs.