Synthesis and characterization of a series of novel platinum coordination complexes of the type cis-[platinum(ammonia)(2)(N-Het)chlorine]nitrate with methyl-substituted thiazoles and benzothiazoles

Cisplatin, cis-diamminedichloroplatinum(II), was the first inorganic compound to show antitumoral properties. Various unrelated Pt(II) and Pt(IV) compounds are active in a wide variety of cancers. Five new compounds were synthesized and characterized; these were of the type cis-[Pt(NH₃)₂(N-Het)Cl]NO₃, where N-Het = 5-methylthiazole (1); 4,5-dimethylthiazole (2); 2-methylbenzothiazole (3); 2,5-dimethylbenzothiazole (4) and; 2,5,6-trimethylbenzothiazole (5). The products were characterized mainly by means of Elemental Analysis (EA) and 1H-NMR, UV-VIS and IR spectroscopy. The EA results showed the complexes were obtained with a high purity; the difference between the %Carbon determinations and the theoretical value was as low as 0.01% and in all cases less than 0.5%. All signals in the 1H-NMR spectra of the ligands shifted downfield upon complexation. Chemical shifts changes were as high as 1.12ppm for the aromatic protons and as high as 0.83ppm for the methyl protons. The wavelengths of the bands of maximum absorption in the UV spectra of the ligands showed a batochromic shift as high as 25nm and the extinction coefficients of the electronic transitions of the ligands changed as much as 101 after complexation to the Pt atom. As for IR spectroscopy, most of the bands of the Mid-IR spectra of the ligands were observed in the spectrum of the related complex but lower in intensity. In addition, the five new compounds and the thiazole (tz) derivative were submitted for cytotoxic assay and tested against two leukemia cancer cell lines, K562 and HL60. Cytotoxic activity of the complexes was 1 < tz < 2 < 4 ∼ 3 < 5 for K562, and for HL60 the activity pattern was 1 < tz < 3 < 2 ∼ 5 ∼ 4. Complex (5) resulted active against promyelocytic leukemia (HL60).