Synthesis, cytotoxic and urease inhibitory activities of some novel isatin-derived bis-Schiff bases and their copper(ii) complexes

Kinetic, spectral, and other studies establish that hydroxamic acids bind reversibly to active-site nickel ion in jack bean urease. Equilibrium ultracentrifugation studies establish that the molecular weight of native urease is 590 000 ± 30 000 while that of the subunit formed in 6 M guanidinium chloride in the presence of β-mercaptoethanol is ~95 000. Essentially the same subunit molecular weight (~93 000) is found by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, subsequent to denaturation in a guanidinium chloride – β-mercaptoethanol system at various temperatures. Coupled with an equivalent weight of 96 600 for binding of the inhibitors acetohydroxamic acid and phosphoramidate, these results establish securely that urease is a hexamer with one active site per 96 600-dalton subunit. Consistent values for the equivalent weight are obtained by a routine spectrophotometric titration of the active site of freshly prepared urease with trans-cinnamoylhydroxamic acid. General equations are derived which describe spectrophotometric titrations of binding sites of any enzyme with a reversible inhibitor. These equations allow the evaluation of the difference spectrum of the protein–inhibitor complex even when the binding sites cannot readily be saturated with the inhibitor or vice versa.

Download Full-text

Synthesis, crystal structures, and urease inhibitory activities of two azido-bridged polynuclear copper(II) complexes with Schiff bases

Transition Metal Chemistry ◽

10.1007/s11243-008-9146-z ◽

2008 ◽

Vol 33 (8) ◽

pp. 1013-1017 ◽

Cited By ~ 16

Author(s):

Peng Hou ◽

Zhong-Lu You ◽

Lin Zhang ◽

Xiao-Li Ma ◽

Li-Li Ni

Keyword(s):

Crystal Structures ◽

Schiff Bases ◽

Inhibitory Activities ◽

Urease Inhibitory

Download Full-text

Jack bean urease: The effect of active-site binding inhibitors on the reactivity of enzyme thiol groups

Bioorganic Chemistry ◽

10.1016/j.bioorg.2007.02.002 ◽

2007 ◽

Vol 35 (5) ◽

pp. 355-365 ◽

Cited By ~ 68

Author(s):

Barbara Krajewska ◽

Wiesława Zaborska

Keyword(s):

Active Site ◽

Jack Bean Urease ◽

Thiol Groups ◽

Jack Bean ◽

Site Binding ◽

Binding Inhibitors

Download Full-text

Synthesis, antibacterial activities, binding mode analysis and predictive ADME studies of novel 1-(aryl)-2-(1H-imidazol-1-yl)methanones

INTERNATIONAL JOURNAL OF PHARMACEUTICAL EDUCATION AND RESEARCH (IJPER) ◽

10.37021/ijper.v2i2.2 ◽

2020 ◽

Vol 2 (02) ◽

pp. 39-45

Author(s):

Priyanka Chandra ◽

Swastika Ganguly ◽

Rajdeep Dey ◽

Biswatrish Sarkar

Keyword(s):

Antibacterial Activity ◽

Spectral Analysis ◽

Nmr Spectroscopy ◽

Active Compound ◽

Active Site ◽

Antibacterial Property ◽

Binding Mode ◽

Antibacterial Activities ◽

Mode Analysis ◽

Benzoyl Chlorides

Introduction: In the present study a novel series of twelve 1-(aryl)-2-(1H-imidazol-1-yl)methanones 3(a-l) were synthesized and characterised by physicochemical and spectral analysis,viz. elemental analysis, IR spectroscopy, NMR spectroscopy. The antibacterial property of the compounds were examined, in order to develop new broad spectrum antibiotics. Methods: The compounds 3(a-l) were synthesised by reacting the corresponding 2-(aryl)-1H-imidazoles 2 with substituted benzoyl chlorides. Binding mode analysis of the most active compound was carried out. Predictive ADME studies were carried out for all the compounds. Results and Discussions: Among the synthesized compounds, (2-(3-nitrophenyl) (2,4-dichlorophenyl) -1Himidazol-1-yl)methanone 3i exhibited highest antibacterial activity. Binding mode analysis of the highest active compound was carried out in the active site of glucosamine-6-phosphate synthase (2VF5).

Download Full-text

Synthesis, crystal structures and Jack bean urease inhibitory activity of copper(II) complexes with 4-bromo-N′-(2-hydroxy-5-methoxybenzylidene)benzohydrazide

Journal of Coordination Chemistry ◽

10.1080/00958972.2016.1262538 ◽

2016 ◽

Vol 70 (3) ◽

pp. 544-555 ◽

Cited By ~ 11

Author(s):

Jing Wang ◽

Dan Qu ◽

Jin-Xian Lei ◽

Zhonglu You

Keyword(s):

Crystal Structures ◽

Inhibitory Activity ◽

Jack Bean Urease ◽

Jack Bean ◽

Urease Inhibitory

Download Full-text

Jack bean urease (EC 3.5.1.5). V. On the mechanism of action of urease on urea, formamide, acetamide, N-methylurea, and related compounds

Canadian Journal of Biochemistry ◽

10.1139/o80-181 ◽

1980 ◽

Vol 58 (12) ◽

pp. 1335-1344 ◽

Cited By ~ 134

Author(s):

Nicholas E. Dixon ◽

Peter W. Riddles ◽

Carlo Gazzola ◽

Robert L. Blakeley ◽

Burt Zerner

Keyword(s):

Enzymatic Hydrolysis ◽

Mechanism Of Action ◽

Active Site ◽

Ph Dependence ◽

Jack Bean Urease ◽

Nickel Ion ◽

Jack Bean ◽

First Time ◽

Hydrolysis Of ◽

Hydrolysis Of Urea

Acetamide and N-methylurea have been shown for the first time to be substrates for jack bean urease. In the enzymatic hydrolysis of urea, formamide, acetamide, and N-methylurea at pH 7.0 and 38 °C, kcat has the values 5870, 85, 0.55, and 0.075 s−1, respectively. The urease-catalyzed hydrolysis of all these substrates involves the active-site nickel ion(s). Enzymatic hydrolysis of the following compounds could not be detected: phenyl formate, p-nitroformanilide, trifluoroacetamide, p-nitrophenyl carbamate, thiourea, and O-methylisouronium ion. In the enzymatic hydrolysis of urea, the pH dependence of kcat between pH 3.4 and 7.8 indicates that at least two prototropic forms are active. Enzymatic hydrolysis of urea in the presence of methanol gave no detectable methyl carbamate. A mechanism of action for urease is proposed which involves initially an O-bonded complex between urea and an active-site Ni2+ ion and subsequently an O-bonded carbamato–enzyme intermediate.

Download Full-text