MULTIPARAMETRIC CELLULAR PROFILING OF HARMINE ANALOGUES IN H4 AND U87 GLIOMA MODELS

Abstract

Glioblastoma remains difficult to treat because heterogeneous cellular programs sustain proliferation, survival, invasion, and treatment resistance. Harmine, a beta-carboline alkaloid, and structurally related analogues have attracted interest as anticancer scaffolds, but comparative cellular profiling across glioma models remains limited. This study evaluated harmine and ten coded analogues in H4 and U87 glioma models using a multiparametric dataset spanning concentration-dependent viability, apoptosis, oxidative stress, mitochondrial function, caspase activation, cell-cycle distribution, proliferation, clonogenicity, migration, invasion, and autophagy. Cells were profiled across 0-40 µM after 48 hours with three replicates per condition. Dose-response behavior and estimated half-maximal inhibitory concentrations were compared, while responses at 20 µM were integrated using standardized endpoint profiles and principal component analysis. The dataset showed clear concentration-dependent loss of viability accompanied by increased apoptosis, reactive oxygen species, caspase-3/7 activity, and altered mitochondrial and cell-cycle responses. Several analogues also reduced Ki-67 positivity, colony formation, migration, and invasion relative to the parent scaffold. Integrated profiling separated compounds and cell models according to coordinated response patterns rather than viability alone. These findings demonstrate the analytical value of multiparametric screening for prioritizing harmine-derived candidates and provide a reproducible framework for subsequent experimental validation in glioma drug discovery studies.