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, ss.1-13, 2026 (SCI-Expanded, Scopus) identifier

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 μM (SiPc (4)) and 25.52

μM (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 IIα (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 Å, 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.