Synthesis and application of diazenyl sulfonamide-based schiff bases as potential BRCA2 active inhibitors against MCF-7 breast cancer cell line

In this study, a library of novel sulfonamide-based Schiff Bases 3a-j was synthesized in high yield (75 to 89%). The FTIR, ¹H NMR, and ¹³C NMR spectroscopic techniques and mass analysis were used to characterize the synthesized compounds. Their Anticancer activity was assessed in vitro on the breast Cancer (MCF-7) and healthy human breast epithelial (MCF-10 A) cell lines over 48 and 72 h using the MTT assay. Most of the synthesized compounds demonstrated promising activity, with compound 3i showing particularly high efficacy at 48 and 72 h (IC₅₀ = 4.85 ± 0.006 and 4.25 ± 0.009 µM) against the MCF-7 breast Cancer cell line. Furthermore, molecular docking studies were performed for compounds 3a-j with the PDB: (3UV7) protein of the breast Cancer susceptibility gene 2 (BRCA2). The obtained results revealed that compound 3i has the strongest binding affinity energy (-7.99 kcal/mol), consistent with the obtained experimental data. Additionally, molecular dynamics (MD) simulation assays confirm the formation of a stable 3i-BRCA2 complex with strong binding affinity through the formation of hydrogen bonds. Antioxidant activities were determined by in vitro assay DPPH cation radical activity method. Interestingly, the compound 3j (IC₅₀ = 12.36 ± 0.55 µM) had comparable activity with ascorbic acid (IC₅₀ = 13.58 ± 0.38 µM) in the antioxidant assay. The results of this research could potentially contribute to the development of new therapeutic agents useful in fighting caused by breast Cancer.

BRCA2; Cytotoxicity; MCF-7 breast cancer cell line; Sulfonamide-based schiff base; Sulfonamides.