Antitumor and Antimetastatic Activity of a Novel Pyrimidin-4-one Derivative in the B16–F10 Melanoma Mouse Model: A Pilot Study

Abstract

Introduction. Cutaneous melanoma is characterized by a high metastatic potential. The involvement of the epidermal growth factor receptor (EGFR) in melanoma invasion and progression provides a rationale for developing novel EGFR-targeted antimetastatic strategies.

Aim. To evaluate the effect of a novel pyrimidin-4-one derivative (6MPSVan-Na) on the growth, metastasis, and morphology of transplanted B16–F10 melanoma.

Materials and Methods. The study was conducted in male C57BL/6 mice with subcutaneously transplanted B16–F10 melanoma. Animals were randomized into three groups (n=10 per group): the main group (6MPSVan-Na, 18.7 mg/kg, intramuscularly); a negative control (water for injection, intramuscularly); and a positive control group receiving the EGFR tyrosine kinase inhibitor gefitinib (43.4 mg/kg, orally) to confirm model sensitivity to EGFR tyrosine kinase inhibitors. Treatment was administered for five consecutive days starting on the day of tumor transplantation, and the course was repeated after a two-day interval. Evaluated parameters included the latent period, tumor growth dynamics and tumor growth inhibition (TGI, %), lifespan, incidence of macrometastases, and histological analysis of tumor tissue. Statistical analysis employed the Mann–Whitney U test, Fisher's exact test, log-rank test, and ANOVA (significance level α=0.05).

Results. The study confirmed the sensitivity of the B16–F10 melanoma model to the reference drug gefitinib. The experimental compound 6MPSVan-Na demonstrated an antitumor activity profile characterized by sustained tumor growth inhibition in the post-exposure period (TGI ≥ 50 %), a statistically significant increase in mouse lifespan, and a reduced incidence of macrometastases to 20% in the lungs and 30% in lymph nodes (p<0.05). Histopathological analysis of tumors following 6MPSVan-Na treatment revealed features predominantly consistent with necroptosis (extensive necrosis, marked lymphohistiocytic infiltration, formation of a lymphocytic cuff, and development of a connective tissue capsule).

Conclusion. In this pilot study, the novel pyrimidin-4-one derivative 6MPSVan-Na demonstrated both antitumor and antimetastatic activity against B16–F10 melanoma, likely mediated through the induction of necroptosis and stimulation of a tumor-specific immune response. These findings support further investigation of 6MPSVan-Na as a potential antimetastatic agent for melanoma.