Casiopeínas^® is a family of copper complexes with the general formulae [Cu(N-N)(N-O)]NO₃ and [Cu(N-N)(O-O)]NO₃; where N-N = substituted aromatic diimine (2,2’-bipyridine (<em>bipy</em>) or 1,10-phenanthroline (<em>phen</em>)); N-O = α-aminoacidate or a peptide; and O-O = acetylacetonate (<em>acac</em>) or salicylaldehydate. These compounds have shown antiproliferative activity in vitro and antitumor activity in several mouse models with promissory results. Efforts have been done in order to understand the role played by ligands in the biological activity. With the aim of finding out the effect of secondary ligand (N-O or O-O), two of the most active complexes <em>in vitro</em> assays were selected to perform in vivo study on HCT-15 colon adenocarcinoma xenograft model. Both complexes, [Cu(3,4,7,8-tetramethyl-1,10-phen anthroline)(glycinato)]NO₃ (<strong>1</strong>) and [Cu(3,4,7,8-tetramethyl-1,10-phenanthroline)(acetylacetonato)]NO₃ (<strong>2</strong>) share the same diimine ligand and the secondary ligand changes from glycinate (<em>gly</em>) to <em>acac</em>. Results show that 2 is effective to reduce tumor size but <strong>1</strong> does not achieve the values required according to protocols, revealing an important difference between compounds attributable to change of ligand from <em>gly</em> to <em>acac</em>.