Synthesis, structures and Helicobacter pylori urease inhibitory activity of copper(II) complexes with tridentate aroylhydrazone ligands

A series of new copper(II) complexes were prepared. They are [CuL1 (NCS)] (1), [CuCILl]center dot CH3OH (2), [CuCIL2]center dot CH3OH (3), [CuL3(NCS)]center dot CH3OH (4), [CuL4(NCS)]center dot 0.4H(2)O (5), and [CuL5(bipy)] (6), where L-1, L-2, L-3 and L-4 are the deprotonated form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, 4-bromo-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide and 2chloro-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, respectively, L-5 is the dianionic form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra and single crystal X-ray diffraction. The Cu atoms in complexes 1, 2, 3, 4 and 5 are coordinated by the NOO donor set of the aroylhydrazone ligands, and one Cl or thiocyanate N atom, forming square planar coordination. The Cu atom in complex 6 is in a square pyramidal coordination, with the NOD donor set of L-1, and one N atom of bipy defining the basal plane, and with the other N atom of bipy occupying the apical position. Complexes 1, 2, 3, 4 and 5 show effective urease inhibitory activities, with IC50 values of 5.14, 0.20, 4.06, 5.52 and 0.26 mu M, respectively. Complex 6 has very weak activity against urease, with IC50 value over 100 mu M. Molecular docking study of the complexes with the Helicobacter pylori urease was performed. The relationship between structures and urease inhibitory activities indicated that copper complexes with square planar coordination are better models for urease inhibition. (C) 2016 Elsevier Inc. All rights reserved.