Synthetic derivatives of natural cinnamic acids as potential anti-colorectal cancer agents

Cinnamic acid and its derivatives represent attractive building blocks for the development of pharmacological tools. A series of piperoniloyl and cinnamoyl-based amides (6-9 a-f) have been synthesized and assayed against a wide panel of colorectal cancer (CRC) cells, with the aim of finding promising anticancer agents. Among all twenty-four synthesized molecules, 7a, 7e-f, 9c, and 9f displayed the best antiproliferative activity. The induced G1 cell cycle arrest and the increase in apoptotic cell death was seen in FACS analysis and western Blotting in the colon tumor cell lines HCT116, SW480, LoVo, and HT29, but not in the nontumor cell line HCEC. In particular, 9f overcame the resistance of HT29 cells, which have a mutant p53 and BRAF. Furthermore, 9f, amide of piperonilic acid with the 3,4-dichlorobenzyl substituent upregulated p21, which is involved in cell cycle arrest as well as in apoptosis induction. Cinnamic acid derivatives might be potential anticancer compounds, useful for the development of promising anti-CRC agents. Twenty-four new derivatives of natural cinnamic acids were designed and synthesized as promising anti-colorectal cancer agents. Their activity was evaluated against HCT116, SW480, HT29, LoVo, and DLD1 cells, in which they induce apoptosis.image