JOURNAL OF INORGANIC BIOCHEMISTRY, cilt.283, ss.1-13, 2026 (SCI-Expanded, Scopus)
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.