Inhibition studies of Jack bean urease with hydrazones and their copper(II) complexes

Abstract

A series of copper(II) complexes, [CuCl2(HL1)]·CH3OH (1), [CuL2(ONO2)] (2), [CuBrL2] (3) and [CuL3(NCS)(CH3OH)] (4) were prepared from 3,5-dihydroxy-N′-(pyridin-2-ylmethylene)benzohydrazide (HL1), 2-hydroxy-N′-(1-(pyridin-2-yl)ethylidene)benzohydrazide (HL2) and 4-methoxy-N′-(pyridin-2-ylmethylene)benzohydrazide (HL3). The compounds were characterized by physico-chemical methods. Structures of HL1 and the complexes were further confirmed by single crystal X-ray diffraction. The metal atoms in complexes 1 and 4 display square pyramidal coordination, in complexes 2 and 3 display square planar coordination. The inhibitory effects of the compounds on Jack bean urease were evaluated. The results showed that the hydrazone HL1 and complexes 1 and 4 have significant urease inhibitory activities, with IC50 values of 8.2 ± 1.5, 6.3 ± 1.7, and 3.1 ± 1.2 μmol·L−1, respectively. Complexes 2 and 3 show medium urease inhibitory activities, with IC50 values of 35.7 ± 3.1, and 41.5 ± 2.7 μmol·L−1, respectively. Molecular docking study of the compounds with Jack bean urease was performed to study the probable binding modes. The compounds with effective urease inhibitory activities anchor well in the active center of the urease and extend to the entrance of the binding pocket by interacting with its key amino acid residues. The results endorse that the hydrazone compound HL1 and complexes 1 and 4 may serve as structural templates for the design and development of novel urease inhibitors.