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Screening of the Antiproliferative Activity of Novel Cu (II) Complex: Comparison of 2D and 3D Cell Culture Models in vitro

The first ideas about the antitumor effect of copper complexes appeared in the 1960s. The biological activity of these complexes is highly dependent on the nature of the ligand. The focus of our research is the new Cu (II) complex with chromone-2-carboxylic acid. The copper (II) complex was synthesized from Cu(NO3)2 x 3H2O and chromone-2-carboxylic acid as ligand. After synthesis, using classical solution chemistry in the stoichiometric ratio (1:1, metal: ligand), the compound was dissolved in DMSO (10-3 mol/dm3) and subjected to cytotoxic appraisal. Evaluated copper(II) complex suppresses cell growth of Hep- G2 cells at highest concentration (10-5 M) by 64.8 % followed by NCI-H358, MRC5 and HT-29 (45.6 % ; 45.3 % ; 43.4 %). The inhibitory effect of copper (II) complex on KATO III, MDAMB 231 and Caco-2 cell lines is less than 25 % indicating low antiproliferative efficacy. The activity of the pure ligand was also tested using the MTT test, and the percentage of survival of all cell lines was more than 95 %. The biological activity of the Cu (II) coordination complex with chromone-2- carboxylic acid was also tested in 3D cell culture (Caco-2 ; HT-29 ; MRC-5). The results after a single treatment on the Caco-2 cell line showed that the complex has an inhibitory effect of 55 % at a concentration of 10-6 mol/dm3 and a 65 % inhibitory effect at a concentration of 10-5 mol/dm3 . The action of the complex on the same cell line during repeated treatment showed a lower inhibitory effect: about 20 % at a concentration of 10-6 mol/dm3 , and about 30 % at a concentration of 10-5 mol/dm3 . During a single treatment, the tested complex inhibits the growth of the HT-29 cell line by about 50 % at a concentration of 10-6 mol/dm3 while it shows extremely high activity on that cell line at a concentration of 10-5 mol/dm3 (cca. 80 %). The action of the complex on the same cell line during repeated treatment again showed a lower inhibitory effect: about 30 % at a concentration of 10-6 mol/dm3 , and about 60 % at a concentration of 10-5 mol/dm3 . The tested complex did not show a significant cytotoxic effect on the MRC-5 cell line in any type of treatment, at any concentration. Theresults clearly indicate that the novel copper (II) complex may represent a promising structural starting point for the development of a new generation of potential antitumor agents.

3D cell models ; NMR ; copper(II) complex

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