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Updated: Jun 29, 2026
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Suppression of glioblastoma progression by novel Phthalocyanine derivatives: In vitro characterization and molecular
Şuranur Ayvaz1, Nevzat Batan1, Cihan İnan1
1Karadeniz Technical University, Faculty of Science, Department of Molecular Biology and Genetics, 61080 Trabzon, Türkiye.
Abstract:
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 dark-condition 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.
Insights
Novel phthalocyanine derivatives show potential against glioblastoma multiforme (GBM) cells in the dark. These compounds reduced cancer cell viability and migration, suggesting new therapeutic avenues for this aggressive brain tumor.
Area of Science:
- Medicinal Chemistry
- Oncology
- Materials Science
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis due to recurrence and treatment resistance.
- Novel therapeutic strategies are needed to target alternative pathways in GBM.
- Phthalocyanines offer versatile chemical scaffolds with potential biological applications.
Purpose of the Study:
- To synthesize and evaluate novel water-soluble silicon (IV) phthalocyanine (SiPc) and boron subphthalocyanine (SubPc) derivatives for their in vitro biological effects under dark conditions.
- To assess the antiproliferative and anti-migratory effects of these compounds on U-87 MG glioblastoma cells.
- To explore potential molecular targets, including focal adhesion kinase (FAK) and DNA topoisomerase IIα (TOP2A), using molecular docking.
Main Methods:
- Synthesis of novel water-soluble SiPc and SubPc derivatives via cyclotetramerization and quaternization.
- In vitro assessment of antiproliferative effects using MTT assays and colony formation assays.
- Evaluation of cell migration inhibition using scratch assays.
- Molecular docking simulations against FAK and TOP2A.
Main Results:
- Synthesized SiPc (4) and SubPc (5) derivatives demonstrated time- and dose-dependent antiproliferative effects on U-87 MG cells.
- Significant inhibition of cell migration and clonogenic capacity was observed.
- Molecular docking predicted favorable binding interactions of both compounds with FAK and TOP2A active sites, with SiPc (4) showing a stronger profile.
Conclusions:
- The novel SiPc and SubPc derivatives exhibit promising dark-condition in vitro activity against U-87 MG glioblastoma cells.
- The compounds effectively reduce cell viability, migration, and colony formation.
- Molecular docking provides a basis for understanding potential mechanisms of action, guiding future research into these phthalocyanine derivatives as potential GBM therapeutics.
