Synthesis of oxamide-hydrazone hybrid derivatives as potential anticancer agents.

BACKGROUND AND PURPOSE: Considering various studies implying anticancer activity of the hydrazone and oxamide derivatives through different mechanisms such as kinases and calpain inhibition, herein, we report the synthesis, characterization, and evaluation of the antiproliferative effect of a series of hydrazones bearing oxamide moiety compounds ( 7a-7n ) against a panel of cancer cell lines to explore a novel and promising anticancer agent ( 7k ).

EXPERIMENTAL APPROACH: Chemical structures of the synthesized compounds were confirmed by FTIR, 1 H-NMR, 13 C-NMR, and mass spectra. The antiproliferative activity and cell cycle progression of the target compound were investigated using the MTT assay and flow cytometry.

FINDINGS/RESULTS: Compound 7k with 2-hydroxybenzylidene structure was found to have a significant in vitro anti-proliferative influence on MDA-MB-231 (human adenocarcinoma breast cancer) and 4T1 (mouse mammary tumor) cells as the model of triple-negative breast cancer, with the IC50-72h values of 7.73 ± 1.05 and 1.82 ± 1.14 μM, respectively. Following 72-h incubation with compound 7k , it caused MDA-MB-231 cell death through G1/S cell cycle arrest at high concentrations (12 and 16 μM).

CONCLUSION AND IMPLICATIONS: Conclusively, this study for the first time reports the anti-proliferative efficacy of compound 7k possessing 2-hydroxyphenyl moiety, which may serve as a potent candidate in triple-negative breast cancer treatment.