2-Formylpyridine 4-Allylthiosemicarbazone Copper(II) Complexes: Enhanced Anticancer Activity against THP-1 Cells

Despite significant advances in cancer therapy, the development of novel selective anticancer agents remains an important research priority. Among various classes of bioactive compounds, thiosemicarbazones have attracted considerable attention because of their structural versatility and promising antiproliferative activity against different cancer cell lines. In this context, the THP-1 human monocytic leukemia cell line represents a relevant model for investigating the anticancer potential of newly developed thiosemicarbazone derivatives and their metal complexes. The aim of this study was to synthesize 2-formylpyridine 4-allylthiosemicarbazone (HL) and its copper(II) complexes and to investigate their anticancer activity against the THP-1 human monocytic leukemia cell line.

For this purpose, the HL was synthesized by the reaction between 4-allylthiosemicarbazide with 2-formylpyridine in ethanol. To obtain the copper(II) complexes [Cu(L)(Cl₂CHCOO)]₂ and [Cu(L)(NO₃)]₂, the ligand reacted with copper(II) dichloroacetate monohydrate and copper(II) nitrate trihydrate in a 1:1 molar ratio in ethanol. All obtained compounds were characterized using modern physicochemical analysis techniques.

The anticancer activity of these compounds against the human acute monocytic leukemia THP-1 cell line was evaluated using the MTS assay. The ligand demonstrated good activity, with an IC₅₀ value 0.11 µM, while its coordination to the copper(II) ion resulted in a significant enhancement of the activity of the corresponding complexes by 15 - 17-fold.

Overall, the obtained results demonstrate that coordination of the 2-formylpyridine 4-allylthiosemicarbazone ligand with copper(II) significantly enhances its anticancer activity against THP-1 cells, highlighting copper complexes as promising candidates for further investigation as potential anticancer agents.

This work was fulfilled with the financial support of the Bilateral Research Project 26.80013.8007.02MDTR, funded by NARD.