Evaluation of Coumarin and Triazole Derived Heterocyclic Compounds in Glioblastoma Cells Using In Vitro and In Silico Approaches
MOKAD 2026 (XI. Multidisipliner Kanser Araştırma Kongresi), İstanbul, Türkiye, 2 - 05 Temmuz 2026, ss.1, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: İstanbul
- Basıldığı Ülke: Türkiye
- Sayfa Sayıları: ss.1
- Karadeniz Teknik Üniversitesi Adresli: Evet
Özet
Introduction and Aim: Glioblastoma is an aggressive
primary brain tumor with invasive growth and limited treatment response.
Myeloid cell leukemia 1 (MCL-1), an anti-apoptotic B-cell lymphoma 2 family
protein, contributes to cancer cell survival and is considered a therapeutic
target. In this study, we evaluated three coumarin-based 1,2,4-triazole Schiff
base derivatives as potential MCL-1-targeting antitumor candidates in U87
glioblastoma cells using in silico and in vitro approaches.
Materials and Methods: Compounds 1, 2 and 3 were
synthesized and characterized according to the reported protocol for triazole
and coumarin-derived heterocyclic compounds [1]. Potential MCL-1 inhibitory
activity was evaluated by activity prediction and molecular docking using
S63845 as the reference ligand [2]. U87 and HaCaT cells were treated
with 1–128 µM compounds for 24, 48, and 72 h, and cell viability was determined
by MTT assay. Colony formation and wound healing assays were performed in U87
cells using 72 h IC50 doses as a migration model [3].
Results: Activity prediction suggested
possible MCL-1 inhibitory potential for compounds 1, 2 and 3. Docking analysis
showed binding energies of −7.7, −8.1, and −7.6 kcal/mol, respectively, while
S63845 showed −8.4 kcal/mol. In U87 cells, 72 h IC50 values were 27.63, 10.98,
and 14.14 µM for compounds 1–3, respectively. The selected doses reduced colony
formation compared with control. Colony diameters decreased from 1374.20±6.34
µm in control cells to 1140.18±8.28, 759.66±5.44, and 797.47±10.42 µm,
respectively. Scratch assay results also indicated reduced wound closure,
particularly in compounds 1 and 2.
Discussion: These findings suggest that the tested coumarin and
triazole-derived heterocyclic compounds may suppress glioblastoma cell
viability, clonogenicity, and migration. Docking findings support a possible
MCL-1-related interaction; however, further molecular validation is required to
confirm target engagement and apoptotic mechanism.
Key words: glioblastoma; MCL-1; coumarin; triazole; docking; migration
Acknowlegdements: This study was supported by the Scientific and Technological
Research Council of Türkiye (TÜBİTAK), ARDEB 1002-A Rapid Support Program,
under project number 225Z193.