Experimental In Vitro and In Vivo Studies of the Antitumor Activity of New Azoloazine Derivatives for the Treatment of Breast Cancer

The search for promising substances aimed at creating new chemotherapeutic drugs based on them is relevant in modern oncology. In this regard, new azoloazine derivatives, which are analogs of the well-known anticancer drug temozolomide, may be promising. The goal was to study the antitumor activity of 11 new azoloazine derivatives in vitro and in vivo. The MTT assay was used to assess the cytotoxic effect of the azoloazines on MCF-7 and CHO cells. BALB/c mice were orthotopically injected with 10⁶ MCF-7 cells to simulate a xenogenic model of breast cancer. The test substances were administered at doses 1/2 IC₅₀ once intraperitoneally 72 hours after tumor transplantation. The degree of differentiation and tumor extent in the tissue and the nature of metastasis were studied by analyzing histological sections of animals removed from the experiment. The volume of the primary tumor was measured. An evaluation of the cytotoxic activity of the new azoloazine derivatives showed that compounds 4, 6, and 9 were the most toxic to MCF-7 cells. Therefore, they were selected for cytotoxicity studies on normal cells (cultured CHO cells). Selected compounds 6 and 9 had low cytotoxicity against CHO cells, which was regarded as a positive aspect for their use as anticancer drugs. An in vivo experiment showed that administration of selected compounds 4, 6, and 9 led to more pronounced inhibition of tumor growth than the use of epirubicin alone. Histological analysis also revealed that compounds 4, 6, and 9 exhibited antitumor activity. The antitumor effects of the new azoloazine derivatives obtained in in vitro and in vivo experiments proved their high activity as potential chemotherapeutic agents and their prospects for further studies aimed at creating new antitumor drugs based on them.