Synthesis, characterization and antitumor activity of cis- bis(acylthioureato) platinum(II) complexes, cis-[PtL2][HL 1=N,N-diphenyl-N′-benzoylthiourea or HL2 = N,N-diphenyl-N′-(p-nitrobenzoyl)thiourea]

Abstract

Acylthiourea ligands, N,N-diphenyl-N′-benzoylthiourea (HL 1) and N,N-diphenyl-N′-(p-nitrobenzoyl) thiourea (HL 2) were prepared in high yields (HL1: 90%, HL2: 82%), by converting benzoyl chloride or p-nitrobenzoyl chloride into the corresponding benzoyl isothiocyanate followed by reacting with diphenylamine. The cis-[PtL2] complexes have been synthesized by reaction of the ligands HL1 or HL2 with K2PtCl4 in a Pt:HL (1:2) molar ratio, in the presence of sodium acetate. The ligands and their cis-[PtL2] complexes have been characterized by elemental analysis, IR, FAB(+)-MS,1H-NMR, 13C-NMR and 195Pt-NMR. The molecular structure of cis-bis(N,N-diphenyl-N′- benzoylthioureato) platinum(II) shows a square-planar geometry with two deprotonated ligands (L1) coordinated to Pt(II) through the oxygen and sulfur atoms in a cis arrangement. The antitumor activity of the ligands and their cis-[PtL2] complexes was evaluated on mouse mammary adenocarcinoma TA3. The IC50 values of culture growth for ligands HL1 and HL2 were 23.1 and 34.9 μM, respectively, whereas for the cis-[PtL2] complexes they were in the range of 2.6-2.8 μM, which indicates that the platinum(II) complexes are about 10-fold more cytotoxic than the free ligands and a participation of nitro group in the complex activity is slightly relevant.