| Sumario: | 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.
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