Design, Synthesis and Anti-Tumor Activity Evaluation of Novel 3,4-(Methylenedioxy)cinnamic Acid Amide-Dithiocarbamate Derivatives.

The fragments, 3,4-(methylenedioxy)cinnamic acid amide and dithiocarbamates, have received increasing attention because of their multiple pharmacological activities in recent years, especially in anti-tumor. We synthesized 17 novel 3,4-(methylenedioxy)cinnamic acid amide-dithiocarbamate derivatives based on the principle of pharmacophore assembly and discovered that compound 4a displayed the most potent antiproliferative activity against HeLa cells with IC value of 1.01 μM. Further mechanistic studies revealed that 4a triggered apoptosis in HeLa cells via activating mitochondria-mediated intrinsic pathways and effectively inhibited colony formation. Also, 4a had the ability to arrest cell cycle in the G2/M phase as well as to inhibit the migration in HeLa cells. More importantly, acute toxicity experiments showed that 4a had good safety in vivo. All the results suggested that compound 4a might serve as a promising lead compound that merited further attention in future anti-tumor drug discovery.