Comprehensive Experimental and Computational Characterization of a Phenylacetamide-Based Molecule.

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Computational Chemistry

Background:

• Neuroblastoma is a pediatric cancer with limited treatment options.
• Tetrahydroisoquinoline derivatives are being explored for therapeutic potential.

Purpose of the Study:

• To synthesize Tetrahydroisoquinoline Derivative 1 (M1).
• To evaluate the biological activities and therapeutic potential of M1 in SH-SY5Y neuroblastoma cells.

Main Methods:

• In silico theoretical calculations using Gaussian software.
• Assessment of M1 activity against cancer-related proteins (PDB IDs: 2F37, 3PBL, 5WIV).
• ADME/T analyses for molecule-likeness.
• MTT assay for cytotoxic activity.
• RT-PCR for gene expression analysis (apoptosis and DNA repair).
• Enzyme activity assays (G6PDH, catalase).

Main Results:

• M1 exhibited maximum cytotoxicity in SH-SY5Y cells after 72 hours.
• M1 significantly reduced cell viability and modulated G6PDH and catalase activities.
• M1 altered the expression of key genes involved in apoptosis (MYC, CASP2, BAX, NF-κB1) and DNA repair (TP53, RAD51, BRCA2, MDM2).

Conclusions:

• Tetrahydroisoquinoline Derivative M1 demonstrates potent cytotoxic activity against neuroblastoma cells.
• M1 influences oxidative stress pathways and gene expression related to apoptosis and DNA repair.
• M1 shows promise as a novel therapeutic candidate for neuroblastoma treatment.