The synthesis, spectroscopic, X-ray characterization and in vitro cytotoxic testing results of activity of five new trans-platinum(IV) complexes with functionalized pyridines

Platinum(IV) complexes with general formulas [Pt(L1−2)2Cl4], where L1−2 are 3-acetylpyridine (1) and 4-acetylpyridine (2) respectively, and [Pt(HL3−5)2Cl2], where H2L3−5 are 2,3-pyridinedicarboxylic acid (3), 2,4-pyridinedicarboxylic acid (4) and 2,5-pyridinedicarboxylic acid (5) respectively, were prepared by the reaction of K2[PtCl6] with the corresponding ligand in 1:2 M ratio in water. The complexes were characterized by elemental analysis and IR and NMR spectroscopy. The structures of complexes 2 and 5 were determined by X-ray crystallography, which revealed the trans orientation of chloride anions around platinum(IV) in the case of both complexes. The antiproliferative activity was investigated in six tumor cell lines (human cervical carcinoma cells (HeLa), murine melanoma cells (B16), human breast carcinoma cells (MDA-MB-453), human colon carcinoma cells (LS-174), transformed human umbilical vein endothelial cells (EA.hy 926) and murine endothelial cells (MS1)) and in one non-tumor cell line-human fetal lung fibroblast cells (MRC-5). Cytotoxicity studies indicated that Pt(IV) complexes with acetyl-substituted pyridine ligands exhibit significantly higher in vitro antiproliferative activity than the complexes with carboxylato-substituted pyridines. Complexes 1 and 2 showed antiproliferative activity in all tested tumor cell lines, with the highest potential in human endothelial cells EA.hy 926, since they had IC50 values of 13.8 ± 5.8 μM and 23.4 ± 3.3 μM, respectively and were more active than cisplatin. Complexes 1 and 2 exhibited lower toxicity against the non-tumor human lung fibroblast cell line (MRC-5) than against most of the tested tumor cell lines. [Display omitted] ► A series of trans Pt(IV) complexes with functionalized pyridines were synthesized. ► The structure of compounds 2 and 5 was proven by X-ray single crystal analysis. ► The obtained compounds were tested to evaluate their in vitro antitumor activity. ► Compounds 1 and 2 showed the highest potential in human endothelial cells EA.hy 926.