Antiproliferative activity of Fe(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes of dithiocarbamate: synthesis, structural characterization, and thermal studies.

Abstract

Five new metal complexes of Fe(II) (1), Co(II) (2), Ni(II) (3), Cu(II) (4), and Zn(II) (5), derived from an N-cyclohexyl N-(3,4-dimethoxybenzyl) dithiocarbamate ligand, have been successfully synthesized and fully characterized by different analytical techniques i.e. elemental analyses, FT-IR, UV-Vis, 1H & 13C NMR, and HRMS. Furthermore, complexes 4 and 5 have been characterized by the SC-XRD technique. Complex 4 adopts a distorted square planar geometry around the Cu(II) center while complex 5 adopts a distorted tetrahedral geometry around the Zn(II) center. In addition, an eight-membered symmetric chair-like metallacycle ring containing two Zn(II) centers has also been found in complex 5. XRD data also show that complexes 4 and 5 are stabilized by various weak intermolecular hydrogen bonding interactions. The course of the thermal degradation of metal complexes 1-5 has been examined by TG-DTA data which revealed that metal sulphide formed as the final residue. Complexes 1-5 demonstrated concentration-dependent cytotoxicity and growth inhibition of DL tumor cells. Among the compounds, complexes 1, 4, and 5 showed significant cytotoxicity and induced a loss in the viability of DL cells. Therapy with complexes 1, 4, and 5 protects DL tumor-bearing animals from exacerbation of the disease, increases lifespan, and significantly improves the histopathological parameters of the vascularized organ, including preventing metastasis. Overall cytotoxicity assay results indicate that all complexes have remarkable cytotoxic potential in comparison with the free ligand.