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, 1H-NMR, 13C-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.

Design and synthesis of novel ureido and thioureido conjugated hydrazone derivatives with potent anticancer activity.

BACKGROUND: Compounds possessing urea/thiourea moiety have a wide range of biological properties including anticancer activity. On the other hand, taking advantage of the low toxicity and structural diversity of hydrazone derivatives, they are presently being considered for designing chemical compounds with hydrazone moiety in the field of cancer treatment. With this in mind, a series of novel ureido/thioureido derivatives possessing a hydrazone moiety bearing nitro and chloro substituents (4a-4i) have been designed, synthesized, characterized and evaluated for their in vitro cytotoxic effect on HT-29 human colon carcinoma and HepG2 hepatocarcinoma cell lines. RESULTS: Two compounds (4c and 4e) having the chloro phenylurea group hybridized with phenyl hydrazone bearing nitro or chloro moieties demonstrated potent anticancer effect with the IC50 values between 2.2 and 4.8 µM at 72 h. The mechanism of action of compound 4c was revealed in hepatocellular carcinoma cells as an inducer of apoptosis in a caspase-independent pathway. CONCLUSION: Taken together, the current work presented compound 4c as a potential lead compound in developing future hepatocellular carcinoma chemotherapy drugs. METHODS: The compounds were synthesized and then characterized by physical and spectral data (FT-IR, 1H-NMR, 13C-NMR, Mass). The anticancer activity was assessed using MTT assay, flowcytometry, annexin-V, DAPI staining and Western blot analysis.