Comprehensive Experimental and Computational Characterization of a Phenylacetamide-Based Molecule

The aim of this study was to synthesize Tetrahydroisoquinoline Derivative 1 (M1) and to evaluate its biological activities in the SH-SY5Y neuroblastoma cell line. Theoretical calculations for the investigated molecule were performed using the Gaussian software package at the B3LYP, HF, and M062X levels with the 6-31g, 6-31++g, and 6-31++g(d,p) basis sets. Subsequently, the activity of the compound against SH-SY5Y cancer-related proteins (PDB IDs: 2F37, 3PBL, and 5WIV) was assessed. In addition, the molecule-likeness properties of the molecule were evaluated through ADME/T analyses. The cytotoxic activity of M1 in the SH-SY5Y cell lines was determined using the MTT assay. Following treatment with M1, the expression levels of apoptosis-related genes (MYC, CASP2, BAX, and NF-κB1) and genes associated with DNA repair mechanisms (TP53, RAD51, BRCA2, and MDM2) were analyzed by RT-PCR. Enzyme activities were also measured in M1-treated SH-SY5Y cells. The results demonstrated that M1 exerted its highest cytotoxic effect in the SH-SY5Y cell line after 72 h of incubation. Compared with the control group, M1 showed a stronger effect on G6PDH activity in SH-SY5Y cells, while catalase activity increased by 78% following M1 treatment. Moreover, M1 markedly reduced cell viability in SH-SY5Y cells relative to the control group. In conclusion, these findings indicate that Tetrahydroisoquinoline Derivative M1 exhibits pronounced cytotoxic activity in SH-SY5Y neuroblastoma cells and significantly modulates oxidative stress-related enzyme activities as well as the expression of genes involved in apoptosis and DNA repair pathways, suggesting that M1 may represent a novel and promising candidate for neuroblastoma therapy.