Synthesis of cinnamic acid ester derivatives with antiproliferative and antimetastatic activities on murine melanoma cells

Melanoma is the most aggressive skin cancer, and its incidence has continued to rise during the past decades. Conventional treatments present severe side effects in cancer patients, and melanoma can be refractory to commonly used anticancer drugs, which justify the efforts to find new potential anti-melanoma drugs. An alternative to promote the discovery of new pharmacological substances would be modifying chemical groups from a bioactive compound. Here we describe the synthesis of seventeen compounds derived from cinnamic acid and their bioactivity evaluation against melanoma cells. The compound phenyl 2,3-dibromo-3-phenylpropanoate (3q) was the most effective against murine B16-F10 cells, as observed in cytotoxicity and cell migration assays. Simultaneously, this compound showed low cytotoxic activity on non-tumor cells. At the highest concentration, the compound 3q was able to trigger apoptosis, whereas, at lower concentrations, it affected the cell cycle and melanoma cell proliferation. Furthermore, cinnamate 3q impaired cell invasion, adhesion, colonization, and actin polymerization. In conclusion, these results highlight the antiproliferative and antimetastatic potential of cinnamic acid derivatives on melanoma.

Automated summary

Melanoma, the most aggressive skin cancer, has been increasing in incidence over the past decades. Conventional treatments have severe side effects and melanoma can be resistant to commonly used anticancer drugs, necessitating the search for new potential anti-melanoma drugs. In this study, we synthesized seventeen compounds derived from cinnamic acid and evaluated their bioactivity against melanoma cells. Phenyl 2,3-dibromo-3-phenylpropanoate (3q) was found to be the most effective compound against murine B16-F10 cells, showing cytotoxicity and inhibitory effects on cell migration. It also had low cytotoxicity on non-tumor cells. Additionally, compound 3q induced apoptosis at high concentrations, while affecting cell cycle and melanoma cell proliferation at lower concentrations. Furthermore, cinnamate 3q inhibited cell invasion, adhesion, colonization, and actin polymerization. These results demonstrate the antiproliferative and antimetastatic potential of cinnamic acid derivatives on melanoma.