In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: Synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents

• DOI: 10.1016/j.ejmech.2008.08.007
• Publication Date: 2008-09-01T05:27:25Z
• Authors: Dimitra Kovala-De...; Athanassios Papag...; Leuteris Papathan...; Alexandros Alexan...; Panagiotis Dalezis; John R. Miller; Mavroudis A. Deme...
• Keywords: Models, Molecular; Thiosemicarbazones; crystal structure; Spectrum Analysis; thiosemicarbazonato complexes; biological evaluation; Antineoplastic Agents; Platinum Compounds; assay; Crystallography, X-Ray; 01 natural sciences; 0104 chemical sciences; 3. Good health; 4n-ethyl thiosemicarbazone; palladium(ii) complexes; spectral properties; biological-activity; platinum(ii) complexes; derivatives; in vitro and in vivo antitumor activity; antifungal; Cell Proliferation

Reactions of thiosemicarbazones of 2-formyl and 2-acetyl pyridine and containing an azepane ring (hexamethyleneiminyl ring) incorporated at N(4)-position, HL(1) (1) and HL(2) (2) with platinum(II) afforded the complexes, [Pt(L(1))Cl] (3) and [Pt(L(2))Cl] (4). Characterization of the compounds was accomplished by means of elemental analysis and spectroscopic techniques NMR, UV-vis and IR spectroscopy. The single-crystal X-ray structure of complex [Pt(L(2))Cl] (4) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N atom, the imine-N atom, and thiolato S-atom. Compounds 1-4 have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). Ligand 2 exhibited high activity as anticancer agent against all four cancer cell lines, while ligand 1 exhibited selectivity against MCF-7, L-929 cell lines and complex 4 against A-549, T-24 cancer cell lines. Also, the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. Complex 3 afforded five to six cures against leukemia P388. The in vivo results of the antitumor activity show the two platinum complexes as very effective chemotherapeutic antileukemic agents.