Synthesis and Enzyme Inhibitory Activities of Ni(II)-Thiosemicarbazone Complexes: [NiC]•2H2O, [NiC], [NiC(H2O)]

Abstract

Three nickel(II) complexes of N(1),N(4)-bis(3-methoxysalicylidene)-S-methylisothiosemicarbazidato chelate were synthesized. These complexes include a hydrated form [NiC]center dot 2H2O, a coordination water-containing form [NiC(H2O)], and a water-free form [NiC]. The compounds were characterized by elemental analysis, IR, UV-Vis, and 1H-NMR spectroscopy, and the crystal structures of two complexes were confirmed by single-crystal X-ray diffraction. The thiosemicarbazone ligand acts as an ONNO-type chelator, forming a stable coordination environment. Square planar geometry was observed for the anhydrous and hydrated complexes, while the coordination water-containing complex exhibited a square pyramidal geometry. The enzyme inhibitory activities of the compounds were evaluated against alpha-amylase, alpha-glucosidase, urease, acetylcholinesterase, elastase, tyrosinase, carbonic anhydrase, and xanthine oxidase. The presence of the nickel center generally enhanced inhibition relative to the free ligand. Differences in enzyme inhibition were observed among the complexes, possibly influenced by structural features such as geometry and solvation state. Among them, the anhydrous complex [NiC] showed the most potent activity, with an alpha-glucosidase IC50 of 759.02 +/- 16.10 mu M, a urease IC50 of 45.68 +/- 2.43 mu M, and a tyrosinase IC50 of 250.92 +/- 12.83 mu M. The cytotoxic activities of the ligand and the complexes were evaluated against healthy cell (HUVEC) by using MTT method, have IC50 values greater than 50 mu M. These findings suggest that variations in hydration and coordination environment may contribute to the observed biological effects.