Synthesis of Novel Cinnamides and a Bis Cinnamate Bearing 1,2,3-Triazole Functionalities with Antiproliferative and Antimetastatic Activities on Melanoma Cells

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.

Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against the Leishmania braziliensis Species

“…In this study, a series of twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments were synthesized. Previous investigations conducted by our research group have identified various bioactive compounds containing benzyl groups with different substitution patterns, linked to 1,2,3-triazolyl moieties [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Additionally, the combination of cinnamic acid with benzylated 1,2,3-triazolyl fragments resulted in compounds with significant antileishmanial effect on L. braziliensis [ 27 ].…”

“…In this study, a series of twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments were synthesized. Previous investigations conducted by our research group have identified various bioactive compounds containing benzyl groups with different substitution patterns, linked to 1,2,3-triazolyl moieties [20][21][22][23][24][25][26]. Addition- Natural products are a valuable resource when exploring therapeutic agents, including for the treatment of leishmaniasis [15].…”

“…In this regard, cinnamic acid is an attractive compound found in several plant species, with a long history of use as human medicine for the treatment of various diseases [16][17][18]. Studies have demonstrated Pharmaceuticals 2023, 16, 1113 3 of 20 the biological activity of cinnamic acid derivatives and 1,2,3-triazole-based compounds, including their leishmanicidal effect [18][19][20][21][22][23][24]. However, few studies have assessed the antileishmanial activity of these compounds against the Leishmania braziliensis species, which is considered the main etiological agent of TL in the Americas.…”