Zuzanna Rzepka, Milena Koch, Beata Izabela Morak-Młodawska, Małgorzata Jeleń, Dorota Małgorzata Wrześniok

Evaluation of the cytotoxic potential of selected 3-methyl-1,6-diazaphenthiazine derivatives in a cellular model of glioma with varying degrees of malignancy

 

2026-09-09

Subject of the study. The subject of the study comprised 3-methyl-1,6-diazaphenothiazine derivatives (B2–B6) containing alkylaminoalkyl and heteroaryl substituents at position 10. These compounds belong to a group of modified phenothiazines that, due to their biological properties, are considered potential anticancer agents. The study included cellular models of glioma, one of the most aggressive tumors of the central nervous system, characterized by high resistance to conventional treatment methods. Cell lines representing different grades of malignancy, as well as normal glial cells, were used in the experiments.

Aim of the study. The aim of this study was to perform a preliminary screening evaluation of the cytotoxic activity of B2–B6 derivatives against glioma cells and to determine their effects on normal human astrocytes. An additional objective was to analyze the lipophilicity parameters of the tested compounds using the SwissADME web server. These properties may influence the biological activity of the compounds and their ability to penetrate biological membranes. In vitro experiments were conducted using U-87 MG and SW-1783 glioma cell lines and normal human astrocytes. Cytotoxicity was assessed using the colorimetric WST-1 assay, which enables the determination of cell viability following exposure to the tested compounds.

Results. The investigated derivatives exhibited diverse cytotoxic activity against glial cells, depending on their chemical structure. The strongest anticancer activity was observed for compounds B3 and B4, which significantly reduced the viability of both U-87 MG and SW-1783 cell lines. At the same time, their effect on normal astrocytes was less pronounced, suggesting a more favorable selectivity profile. The remaining compounds showed weaker activity or affected both cancerous and normal cells to a similar extent. In silico analysis revealed differences in lipophilicity parameters among the tested derivatives.

Conclusions. The B2–B6 derivatives demonstrated moderate but diverse cytotoxic activity against glioma cells in vitro. Compounds B3 and B4 showed the most promising properties, exhibiting greater activity toward cancer cells than toward normal cells. The obtained results indicate the need for further studies on these compounds, including investigations of their mechanisms of action and structural optimization aimed at improving their anticancer efficacy and selectivity.

Keywords: cytotoxicity, astrocytes, glioma, phenothiazines.

© Farm Pol, 2026, 82(3): 119–127