Transition metal complexes (M = Cu, Ni and Mn) of Schiff-base ligands: Syntheses, crystal structures, and inhibitory bioactivities against urease and xanthine oxidase

Six new transition metal complexes (M = Cu(II), Ni(II) and Mn(III)) of tridentate (H2L1, HL2) and/or bidentate (HL3, HL4) Schiff-base ligands, obtained from the condensation of salicylaldehyde with glycine, N-(2-aminoethyl)morpholine, 4-(2-aminoethyl)phenylic acid and 4-(2-aminoethyl)benzsulfamide, respectively, were synthesized and structurally determined by single-crystal X-ray analysis. Complexes 1–6 were evaluated for their effect on the jack bean urease and xanthine oxidase (XO). Copper(II) complexes 1–3 (IC50 = 0.43–2.25 μM) showed potent inhibitory activity against jack bean urease, comparable with acetohydroxamicacid (IC50 = 42.12 μM), which is a positive reference. And these copper(II) complexes (IC50 = 10.26–15.82 μM) also exhibited strong ability to inhibit activity of XO, comparable to allopurinol (IC50 = 10.37 μM), which was used as a positive reference. Nickel(II) and manganese(III) complexes 4–6 showed weak inhibitory activity to jack bean urease (IC50 = 4.36–8.25 μM) and no ability to inhibit XO (IC50 > 100 μM).

Graphical abstractSix new transition metal complexes (M = Cu(II), Ni(II) and Mn(III)) of Schiff base were synthesized and structurally determined by single-crystal X-ray analysis. And these complexes were evaluated for their effect on the jack bean urease and xanthine oxidase (XO). Copper(II) complexes 1–3 not only showed potent inhibitory activity against jack bean urease (IC50 = 0.43–2.25 μM), these complexes also exhibited strong ability to inhibit activity of XO (IC50 = 10.26–15.82 μM). However, nickel(II) and manganese(III) complexes 4–6 showed weak inhibitory activity to jack bean urease (IC50 = 4.36–8.25 μM) and no ability to inhibit XO (IC50 > 100 μM). We have demonstrated for the first time that Schiff-base complexes show urease and XO inhibitory activities. The mechanisms of the inhibitory activity require to be further investigated.Figure optionsDownload full-size imageDownload as PowerPoint slide