Suppression of glioblastoma progression by novel Phthalocyanine derivatives: In vitro characterization and molecular docking analysis

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Ayvaz Ş., Batan N., İnan C., Güler H. İ., Değirmencioğlu İ.

JOURNAL OF INORGANIC BIOCHEMISTRY, cilt.283, 2026 (SCI-Expanded, Scopus)

Özet

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite standard treatment prognosis remains poor due high recurrence and rapid therapeutic resistance, highlighting the need for new agents targeting alternative pathways. Phthalocyanines represent chemically versatile scaffolds with favorable photophysical and structural properties; however, present study focused specifically on their darkcondition in vitro biological effects rather than photodynamic activity. In this study, two novel water-soluble silicon (IV) phthalocyanine and boron subphthalocyanine derivatives were synthesized for the first time via cyclotetramerization, and water-soluble derivatives were obtained by quaternization with methyl iodide (CH3I) in chloroform at room temperature in dark. The antiproliferative and scratch assay-based migration-modulating effects of these compounds were assessed in U-87 MG glioblastoma cells under dark conditions. MTT assays showed time- and dose-dependent decreases in viability, with 72 h IC50 values of 15.46 mu M (SiPc (4)) and 25.52 mu M (SubPc (5)). Colony formation assays indicated marked suppression of clonogenic capacity, and scratch assays demonstrated significant inhibition of migration. To gain mechanistic insight, molecular docking was performed against focal adhesion kinase (FAK) and DNA topoisomerase II alpha (TOP2A); both compounds showed favorable predicted binding to the active sites, with SiPc (4) displaying a stronger interaction profile. Redocking of co-crystallized ligands yielded RMSD values below 2.0 & Aring;, supporting protocol reliability. Overall, these findings suggest preliminary dark-condition in vitro activity of SiPc (Tan et al., 2020 (4)) and SubPc (Weller et al., 2021 (5)) against U-87 MG cells, while the docking results offer hypothesis-generating molecular insight into possible target interactions that may support future mechanistic and optimization studies.