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

• Published in: Biomedicine & pharmacotherapy 2022-04, Vol.148, p.112689-112689, Article 112689
• Main Authors: Vale, Juliana Alves do, Rodrigues, Michelle Peixoto, Lima, Ângela Maria Almeida, Santiago, Samira Soares, Lima, Graziela Domingues de Almeida, Almeida, Alisson Andrade, Oliveira, Leandro Licursi de, Bressan, Gustavo Costa, Teixeira, Róbson Ricardo, Machado-Neves, Mariana
• Format: Article
• Language: English
• Subjects: Animals; Anti-melanoma; Anticancer drug discovery; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumoral activity; B16-F10 cell line; Cell Line, Tumor; Cell Proliferation; Cinnamates; Cinnamates - chemistry; Cinnamates - pharmacology; Cinnamic acid; Esters - pharmacology; Humans; Melanoma - drug therapy; Melanoma, Experimental - drug therapy; Mice
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.112689

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. [Display omitted] •We synthetized seventeen cinnamates derived from trans-cinnamic acid.•The Steglich esterification reaction was the main step involved in their synthesis.•The most effective compound 3q reduced the melanoma cell viability.•Compound 3q caused cell cycle arrest and apoptosis in B16-F10 cells.•This compound also impaired cell invasion, adhesion, and colonization.