Synthesis, characterization and anticancer activity of new 2-acetyl-5-methyl thiophene and cinnamaldehyde thiosemicarbazones and their palladium(II) complexes

Abstract

New thiosemicarbazone (TSC) ligands, AMT-CN-TSCH (L1), AMT-CN-TSC(CH3) (L2), CIN-CN-TSCH (L3) and CIN-CN-TSC(CH3) (L4) (AMT = 2-acetyl-5-methylthiophene, TSCH = thiosemicarbazide, TSC(CH3) = 4-methyl-3-thiosemicarbazide, CIN = cinnamaldehyde) were synthesized by condensation reaction. The reaction of [PdCODCl2] with the ligands L1, L2 and L4in the ratio 1:1 yielded complexes [Pd(L1)Cl] (C1), [Pd(L2)Cl2] (C2), and [Pd(L4)2Cl2] (C4) respectively (COD = 1,5-cyclooctadiene). The reaction of [Pd(COD)Cl2] with CIN-CN-TSCH (L3) in 1:2 metal to ligand ratio yielded the complex [Pd(L3)2] (C3). The ligands and the complexes were characterized by UV–Vis, FT-IR, NMR, elemental analysis and conductivity measurements. The ligand L1 coordinated to the metal in a tridentate fashion while L2, L3 and L4 coordinated in a bidentate fashion. The ligands L1 and L3 coordinated to the metal as thiol anions while ligand L4 coordinated via the thione sulphur. Conductivity measurements of the metal complexes in dimethyl sulfoxide showed that the chloride ions complexes C1, C2 and C4 are within the coordination spheres. The crystal structures of ligands L2 and L4 were obtained from a Bruker Smart KAPPA APEXII DUO diffractometer with graphite monochromated Mo Kαradiation (k = 0.71073 Å). Cytotoxic activity of the compounds was investigated against the human cancer cell lines; Caco-2 (colon), HeLa (cervical), Hep-G2 (hepatocellular), MCF-7 (breast), PC-3 (prostate) and MCF-12A (non-cancer breast) cells. The complex C2 exhibited excellent broad spectrum growth inhibition activity against all the human cell lines tested except for the non-cancer breast cells. All the metal complexes synthesized inhibited the proliferation of human prostate cancer cell.