Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice

Abstract

Breast cancer (BC) is one of the most common types of malignant tumors, which makes scientific research in this area extremely relevant. The difficulties of breast cancer chemotherapy stimulate the search for new drugs to treat this nosology. Derivatives of imidazotriazine and imidazotetrazine, which are analogues of the antitumor drug temozolamide, can be ones of the promising drugs in this regard.The aim of the work was to evaluate the antitumor activity of three new azoloazine derivatives in a xenogeneic breast cancer model in mice in vivo.Materials and methods. A study was conducted on a xenogeneic model of BC. After the immunosuppression with azathioprine, 48 white BALB/c mice were injected with MCF-7 cells, test derivatives, and the reference drug epirubicin at doses of 1/2 IC50 and 1/10 IC50, into the base of the mammary gland once. The body weight of the mice was monitored; on the 15th day, at the end of the experiment, the relative volume was assessed.Results and discussion. Among the three compounds studied, imidazotetrazine 1 showed the most encouraging results: stopping the loss of body weight in the mice caused by the administration of tumor cells, and reducing the tumor volume on the 15th day of the experiment to 50.6% of that in the control when using a dose of 1/10 IC50, up to 39.2% – when using a dose of 1/2 IC50, which significantly exceeded the values of the reference drug epirubicin and the values in the control group. In the histological examination, the signs of spread and preservation of tumor cells viability of the MCF-7 line after its administration were minimal, the value of the histological malignancy index decreased by 9.3% of the control value.Conclusion. Among the tested azoloazine derivatives, 3-cyclohexyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-N-piperidinylcarboxamide is the undisputed leader, causing inhibition of the tumor growth in a xenogeneic model in vivo.