Synthesis and Biological Evaluations of Monocarbonyl Curcumin Inspired Pyrazole Analogues as Potential Anti-Colon Cancer Agent.

PURPOSE

The monocarbonyl analogs of curcumin (MCACs) have been widely studied for their promising antitumor activity. Pyrazole is a five-membered aromatic heterocyclic system with various bioactivities incorporated frequently in drugs. However, few of MCACs inspired pyrazole analogues were investigated. To search for more potent cytotoxic agents based on MCACs, a series of new 1,5-diaryl/heteroaryl-1,4-pentadien-3-ones inspired pyrazole moiety was synthesized and evaluated on their anti-colon cancer activities.

METHODS

Fifteen new compounds were synthesized and characterized by spectral datum, and then they were tested preliminarily by MTT assay for their cytotoxic activities against a panel of four human cancer cell lines, namely, gastric (SGC-7901), liver (HepG2), lung (A549), and colon (SW620) cancer cells. Compound exhibited excellent selectivity and outstanding anti-proliferation activity against SW620 cells among these 15 compounds. Further, the mechanisms were investigated by transwell migration and invasion assay, clonogenic assay, cell apoptosis analysis, cell cycle analysis, Western blot analysis.

RESULTS

The IC value of against SW620 cells was 12 nM, being more potent than curcumin (IC = 9.36 μM), adriamysin (IC = 3.28 μM) and oxaliplatin (IC = 13.33 μM). Further assays showed that inhibited SW620 cell migration, invasion and colony formation obviously, which was due to its ability to induce cell cycle arrest in the G2/M and S phases and apoptosis. Western blot assay revealed that decreased the protein expression of ATM gene, which may primarily contribute to its anticancer activity against SW620 cells.

CONCLUSION

A new MCACs was synthesized and found to exhibit excellent anti-proliferation activity against SW620 cells. Further studies indicated that exerted its anticancer activity against SW620 cells probably via decreasing the ATM protein expression. The present study suggested that was a promising candidate as an anti-colon cancer drug for future development.