Synthesis, Characterization, and Anticancer Evaluation of Novel Nickel(II) and Copper(II) Complexes Derived from Isatin Thiosemicarbazones

The complex of (2,2'-(7,7'-dimethyl-2,2'-dioxo-1,1',2,2'-tetrahydro-3H,3'H-5,5'-biindole-3,3'-diylidene) dihydrazinecarbo thioamide), denoted as L, was prepared by the reaction of o-tolidine with chloral hydrate and hydroxylamine hydrochloride in the presence of sodium sulfate and a co-solvent, absolute ethanol. The novel complexes of Ni(II) and Cu(II) with the ligand, L, have been synthesized from a reaction of one mole of L with two moles of NiCl2 and CuCl2 to produce complexes with the general formula [M2LCl2] [where M= Ni(II) or Cu(II)]. All three complexes are novel and have a square planar geometry. The metal ions in the two metal complexes coordinate with the ligand via nitrogen, oxygen, and sulfur centers. FT-IR spectroscopy, 1H-NMR spectroscopy, UV-visible spectra and elemental analysis (CHNS) studies were employed for characterization. Existing anticancer agents often face limitations and challenges such as resistance and adverse side effects. This study aims to bridge this research gap by synthesizing and characterizing novel nickel(II) and copper(II) complexes as potential anticancer agents and evaluating their in vitro anticancer activity against the MCF-7 breast cancer cell line. Both compounds proved to be more potent against the MCF-7 cell line than widely used anticancer drug cisplatin. In assessing in vitro anti-proliferative activity against the MCF-7 cell line, [Cu2(L)Cl2] exhibited notable cytotoxicity, with an IC50 of 8.43 µM (5.53 µg/mL), surpassing cisplatin (34.29 µM or 10.29 µg/mL). The IC50 for [Ni2 (L)Cl2] was 26.73 µM (17.45 µg/mL). These results highlight the potential of [Cu2(L)Cl2] as a promising candidate for further investigation in cancer treatment.