New thiosemicarbazones and their palladium(II) complexes: Synthesis, spectroscopic characterization, X-ray structure and anticancer evaluation

Thiosemicarbazones (TSCs) have proven to be an important group of N[sbnd]S donor Schiff base ligands. Their biological activities, structural and donor diversities are often improved after coordination to a metal ion. In this work, novel thiophene-based thiosemicarbazone ligands; (E)-N,N’-dimethyl-2-((5′-methyl-[2,2′-bithiophen]-5-yl)methylene)hydrazine-1-carbothioamide (L1), (E)-N-ethyl-2-((5-phenylthiophen-2-yl)methylene)hydrazine-1-carbothioamide (L2) and (E)-2-((5′methyl)-[2,2′-bithiophen]-5-yl)methylene)-N-phenylhydrazine-1-carbothioamide (L3) were synthesized via condensation reaction. The corresponding complexes (C1, C2 and C3) were synthesized by reacting the ligands with Pd(cod)Cl2 under inert nitrogen environment. All the prepared ligands and complexes were characterized by using the FTIR, UV–Vis, 1H and 13C NMR, elemental analysis and single crystal X-ray crystallography on ligand L2. The anticancer activities of the complexes were investigated against human the Caco-2, HT-29, HeLa and non-cancerous KMST-6 cell lines. In the preliminary studies, unexpectedly of all ligands and complexes, L1 showed the best anti-tumor activities at 100 µg/mL with cell viabilities < 31% in all the cell lines. In general, cell lines were more susceptible to complexes than free ligands except for C1. Complex C2 had the highest activity among complexes; HeLa (8.4%), HT-29 (8.8%), Caco-2 (16.1%) and KMST-6 (24.5%) cell viabilities at a concentration of 100 µg/mL. The C3 complex demonstrated appreciable selectivity since it had minimal effect on non-cancerous KMST-6 cell line (76%) with relatively reduced cytotoxicity in other cells except in HeLa (0.0%). All the complexes prepared inhibited proliferation of HeLa cells.