Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i) and Tc(i) thiazole-based complexes.

A new thiazole-containing multidentate ligand 2-((2-phenylthiazol-4-yl)methylthio)ethanamine, L, was synthesized and used to prepare new complexes of the formula PdLCl (Pd-L), CuLCl (Cu-L) and -[Re/Tc(CO)(L)] (Re/Tc-L). The ligand L and the metal complexes were characterized spectroscopically. Furthermore, the structures of Re-L and Cu-L were elucidated by X-ray crystallography. Ligand L acts as a bidentate (N, S) chelator in Pd-L, as a bidentate (N, S) chelator in Cu-L and as a tridentate (N, S, N) chelator in Re-L. The radiotracer Tc-L was synthesized in high yield and characterised by HPLC comparison with the Re-L analog. The synthesized compounds were evaluated for their anti-inflammatory and cytotoxic properties. The compounds exhibited low anti-inflammatory activity with Pd-L showing the highest activity among them. The cytotoxic activity of the ligand and the complexes against several human cancer cell lines (cervical adenocarcinoma HeLa, colorectal adenocarcinoma LS-174T, lung adenocarcinoma A549, breast adenocarcinoma MDA-MB-231 and normal human lung fibroblast cell line MRC-5) was examined using the MTT assay. The complex Cu-L exhibited the highest cytotoxicity and the complex Pd-L showed the best tumor selectivity. The changes in the cell cycle phase distribution were determined by flow cytometry and it was found that ligand L shows the highest apoptotic activity. The biodistribution studies of Tc-L in mice showed fast tissue clearance. Of all the thiazole-containing compounds, the palladium complex appears to be more promising for future efforts.