Abstract
The present investigation describes the synthesis of novel cinnamides and a bis cinnamate bearing 1,2,3-triazole functionalities and investigation of their antiproliferative and antimetastatic effects on melanoma cells. The necessity for the development of new chemotherapeutic agents for melanoma treatment motivated this work. Sixteen derivatives were obtained with yields ranging from 23-81% and fully characterized by spectroscopic (1H and 13C nuclear magnetic resonance, infrared) and spectrometric high resolution mass spectrometry (HRMS) techniques. The derivatives were in vitro evaluated against B16-F10 murine melanoma cell line. The most effective compound (a bis cinnamate) (6b) reduced the melanoma cell viability, generated cell cycle arrest, and influenced the metastatic behavior of melanoma cells by decreasing migration, invasion, and colony formation. Based on these findings, it is believed that compound 6b may represent an interesting scaffold to be explored toward the development of new antimelanoma agents.
Highlights
The steps involved in the synthesis of cinnamides 3a-3n are outlined in Scheme 1
It was demonstrated that the derivative 6b, the most effective compound, reduced the melanoma cell viability, generated cell cycle arrest, and influenced the metastatic behavior of melanoma cells, by decreasing migration, invasion, and colony formation. These results clearly showed the cytotoxic, antiproliferative and antimetastatic potential of compound 6b against melanoma cells and highlight the cinnamic acid derivative as possible therapeutic target for the treatment of metastatic cancers
Generalities The solvents were purchased from Vetec (Rio de Janeiro, RJ, Brazil), Sigma-Aldrich
Summary
Melanoma is the most serious type of skin cancer.[1,2] It is originated from uncontrolled growth of melanocytes that are dendritic-like cells responsible for skin pigmentation.[3,4] Melanoma accounts for the highest number of skin cancer deaths worldwide, and its incidence rate is increasing over the last years.[5,6,7] In 2020, new melanoma cases in the United States were estimated to be about 100,350 with 6,850 deaths, whereas in Brazil approximately 8,450 new cases were projected.[5,8]Genetic mutations, excessive ultraviolet radiation exposure, severe sunburn, outdoor training, advanced age, and gender are relevant factors related to melanoma susceptibility.[2,9] melanoma has a high tendency to spread to other parts of the body. They have been used as templates for designing and arriving at newly compounds with antitumor activities.[27,28] Our research group reported the preparation of a series of twenty-six cinnamic acid derivatives resulting from the connection of cinnamic acid with 1,2,3-triazole functionalities.[28] In the latter, B16-F10 cell line was used in in vitro assays to evaluate the antimelanoma activity of these compounds.
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