Synthesis, structural characterization and cytotoxicity evaluation of platinum(II) complexes of heterocyclic selenones

Platinum(II) complexes (1–6) with selenones (HLn), having the general formula [Pt(HLn)₄]Cl₂, were prepared and characterized by elemental analysis, IR and NMR (¹H, ¹³C, ⁷⁷Se and ¹⁹⁵Pt) methods and one of them, [Pt(N-ethylimidazolidine-2-selenone)₄]Cl₂ (3) by X-ray crystallography. A decrease in the IR frequency of the >C[dbnd]Se mode and an upfield shift in ¹³C NMR for the >C[dbnd]Se resonance of selenones are consistent with the selenium coordination to platinum(II). The structure of 3 consists of [Pt(L3)₄]²⁺ complex ion and chloride counter ions. The platinum(II) atom in complex cation adopts a distorted square planar geometry. The in vitro antitumor activity of the complexes, as well as cisplatin, were evaluated by MTT assay against human ovarian carcinoma A2780 and its cisplatin-resistant subline A2780R, human prostate cancer 22Rv1 and human breast adenocarcinoma MCF-7 cell lines. The results indicated that only one of the complexes, involving the N-propylimidazolidine-2-selenone (4) ligand, was effective against the A2780 cells (IC₅₀ = 44.7 µM) on the comparable level as cisplatin (IC₅₀ = 26.8 µM). The interaction studies with sulfur-containing biomolecules revealed their ability to form a variety of coordination and recombination intermediates, and oxidized species with L-cysteine and reduced glutathione.