Studies on the Complexation of Platinum(II) by Some 4-Nitroisoxazoles and Testing the Cytotoxic Activity of the Resulting Complexes.

Two novel platinum(II) complexes ( and ) were synthesized by the reaction of the appropriate 3,5-dimethyl-4-nitroisoxazole with KPtCl and characterized by elemental analysis, ESI MS spectrometry, H NMR and far-IR spectroscopy. The structure of complex was additionally confirmed by X-ray diffraction. The cytotoxicity of the investigated compounds was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian and A-549 lung adenocarcinomas) in both normoxia and hypoxia conditions. LogPs of complexes were measured using the shake-flask method. The complex showed much better cytotoxic activity than cisplatin for all the tested cancer cell lines. complex was inferior to its isomer against all the cancer lines tested in normoxia conditions but proved superior to the reference cisplatin against the MCF-7 and A549 lines, and showed similar activity to cisplatin against the ES-2 line. To gain additional information that may facilitate the explanation of the pharmacological activity of the tested compounds, cellular platinum uptake and stability in L-glutathione solution were determined for both compounds and .