Comprehensive Investigation of a Novel Schiff Base: Synthesis, Anticancer Efficacy, Gene Expression Profiling, and...

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Osteosarcoma is a primary bone cancer with limited effective treatments.
• Novel therapeutic agents targeting cancer-specific pathways are urgently needed.

Purpose of the Study:

• To evaluate the anticancer potential of a novel azomethine-based compound (B-134-0) against osteosarcoma (SAOS-2) cells.
• To investigate the compound's effects on apoptosis and DNA damage response (DDR) gene expression.

Main Methods:

• Synthesis and characterization of B-134-0.
• In vitro cytotoxicity assessment using MTT assay.
• Quantitative PCR (qPCR) to analyze gene expression of TP53, RAD51, BRCA2, CASP2, MYC, MDM2, CDKN1A, ERCC1, ATR, and PRKDC.
• Molecular docking and DFT analyses for structural and interaction studies.

Main Results:

• B-134-0 demonstrated significant time-dependent cytotoxicity against SAOS-2 cells (IC50 values decreased with prolonged exposure).
• The compound modulated the expression of cell cycle and DNA repair genes, downregulating TP53, RAD51, CASP2, MYC, and MDM2, while upregulating CDKN1A and BRCA2.
• Molecular docking confirmed strong binding affinity with BRCA2 and CDKN1A, supporting the observed gene expression changes.

Conclusions:

• B-134-0 exhibits potent anticancer activity against osteosarcoma cells.
• The compound effectively modulates DNA damage response and apoptosis pathways.
• B-134-0 shows promise as a potential therapeutic candidate for osteosarcoma treatment due to its efficacy and molecular stability.