Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i) and 99mTc(i) thiazole-based complexes

A new thiazole-containing multidentate ligand 2-((2-phenylthiazol-4-yl)methylthio)ethanamine, L, was syn-thesized and used to prepare new complexes of the formula PdIILCl2(Pd–L), CuIIL2Cl2(Cu–L) andfac-[Re/99mTcIIJCO)3IJL)]+(Re/99mTc–L). The ligand L and the metal complexes were characterized spectroscopically.Furthermore, the structures of Re–LandCu–L were elucidated by X-ray crystallography. Ligand L acts as abidentate (Nth,S)chelatorinPd–L, as a bidentate (N, S) chelator in Cu–Landasatridentate(Nth, S, N) che-lator in Re–L. The radiotracer99mTc–L was synthesized in high yield and characterised by HPLC comparisonwith the Re–L analog. The synthesized compounds were evaluated for their anti-inflammatory and cyto-toxic properties. The compounds exhibited low anti-inflammatory activity with Pd–L showing the highestactivity among them. The cytotoxic activity of the ligand and the complexes against several human cancercell lines (cervical adenocarcinoma HeLa, colorectal adenocarcinoma LS-174T, lung adenocarcinomaA549, breast adenocarcinoma MDA-MB-231 and normal human lung fibroblast cell line MRC-5) was exam-ined using the MTT assay. The complex Cu–L exhibited the highest cytotoxicity and the complex Pd–Lshowed the best tumor selectivity. The changes in the cell cycle phase distribution were determined byflow cytometry and it was found that ligand L shows the highest apoptotic activity. The biodistributionstudies of99mTc–L in mice showed fast tissue clearance. Of all the thiazole-containing compounds, thepalladium complex appears to be more promising for future efforts