Synthesis and biological evaluation of hydroxycinnamic acid hydrazide derivatives as inducer of caspase-3

• Series of novel hydroxycinnamic acid hydrazide were synthesized.
• The anticancer activity was evaluated by MTT methods.
• Compound 2c induced cell cycle arrest at G2/M phase in H1299 cells.
• Caspase-3 mediated pathway is involved in 2c induced apoptosis.

In order to generate compounds with superior antitumor activity and reduced toxicity, twelve new hydroxycinnamic acid hydrazide derivatives were synthesized and evaluated for their antiproliferative activities against two cancer cell lines (H1299 lung carcinoma cells and MCF-7 breast cancer cells), and compared to two normal counterparts (NL-20 lung epithelial cells and H184B5F5/M10 breast cells) by MTT method. The results demonstrated that some of these compounds possessed good antiproliferative activity against the two cancer cell lines. Among them, compound 2c was active against the growth of H1299 lung carcinoma cells with IC50 values of 1.50 μM, which was more active than the positive topotecan (IC50 = 4.18 μM). Simultaneously, it showed lower cytotoxic effects on normal NL-20 lung epithelial cells (IC50 > 10 μM). Mechanism studies indicated that it induced cell cycle arrest at G2/M phase followed by activation of caspase-3, and consequently caused the cell death. Further studies on the structure optimization are ongoing.

Effects of 2c (1.0–3.0 μM) on the activation of caspase-3. Protein loading was normalized to the expression of β-actin. A representative experiment is shown of three performed.Figure optionsDownload as PowerPoint slide