Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1368, 2026 (SCI-Expanded, Scopus)
Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, with limited therapeutic options, highlighting the need for new molecular targets and therapeutic agents. This study describes the synthesis and characterization of two novel series of thiazole-linked hydrazone derivatives (3a-g and 4a-g) and their evaluation as potential human NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors for GBM treatment. Cytotoxicity assays against U87 glioblastoma and L929 normal mouse fibroblast cells identified compounds 3e (IC₅₀ = 9.95 ± 1.08 µM) and 4d (IC₅₀ = 3.27 ± 0.62 µM) as lead molecules with high selectivity indices. Both compounds effectively inhibited NQO1 activity and increased total reactive oxygen species (ROS) levels. Treatment with 3e and 4d induced mitochondrial-mediated apoptosis by elevating Bax expression and reducing Bcl-2 expression, resulting in a higher Bax/Bcl-2 ratio. Molecular docking studies showed that 3e (−9.0 kcal/mol) and 4d (−7.3 kcal/mol) exhibited strong binding affinities for the NQO1 active site, similar to dicoumarol. These findings suggest that 2-thiazolyl hydrazone analogues represent promising leads for further optimization as novel NQO1-targeting agents for GBM.