Complexes of N- and O-Donor Ligands as Potential Urease Inhibitors

Abstract

We report five new transition-metal complexes that inhibit the urease enzyme. Barbituric acid (BTA), thiobarbituric acid (TBA), isoniazid (INZ), and nicotinamide (NCA) ligands were employed in complexation reactions. The resulting complexes were characterized using a variety of analytical techniques including infra-red and UV−vis spectroscopy, 1 H NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. We describe two mononuclear complexes with a general formula {[M(NCA) 2 (H 2 O) 4 ](BTA) 2 (H 2 O)}, where M = Co (1) and Zn (2), a mononuclear complex {[Ni(NCA) 2 (H 2 O) 4 ](TBA) 2 (H 2 O)} (3), and two polymeric chains of a general formula {[M(INZ) (H 2 O) 3 ]-(BTA) 2 (H 2 O) 3 }, where M = Co (4) and Zn (5). These complexes displayed significant urease enzyme inhibition with IC 50 values in the range of 3.9−19.9 μM.

Urease inhibition and molecular docking studies on transition metal complexes of ligands derived from barbituric and thiobarbituric acids

“…The geometry around the Co (II) ion is octahedral, which is slightly distorted. The Co (II) ion is coordinated by one nitrogen 17 The continuous shape measure (CshM) theory, using SHAPE software, 19 was used to calculate the degree of distortion of the coordination polyhedron. The distorted coordination geometry at Co (Figure S6) is very close to an ideal octahedron (O h ), with a value for the deviation from standard O h symmetry of 0.43 (Table S5).…”

“…A mixture containing 200 μl, 25 μl of urease enzyme from Canavalia ensiformis (jack bean), 5 μl of samples at varying concentrations, and 55 μl of urea (100 mM) was incubated in 96-well plates for a duration of 15 min at 30 C. Subsequently, a 45 μl phenol/sodium nitroprusside mixture (1% w/v; 0.005% w/v) and 70 μl of NaOH/ NaOCl alkali mixture (0.5% w/v; 0.1% w/v) were added, and the urease activity was measured using the indophenol method as described by Weatherburn. 17 All reactions were performed in phosphate buffer at 6.8 pH and changes in absorbance were measured at 630 nm with a microplate reader (xMark Microplate Spectrophotometer, BIO-RAD) for 50 min. The assays were repeated three times, and thiourea was employed as a positive control.…”

Synthesis, antimicrobial, antitumor activity, docking simulation, theoretical studies, and electrochemical analysis of novel Cd(II), Co(II), Cu(II), and Fe(III) complexes containing barbituric moiety

“…Furthermore, a one-pot complexation technique makes it simple to combine many organic ligands with known characteristics into a single metal complex. [7][8][9][10][11][12] Barbituric and thiobarbituric acids include the pyrimidine nucleus and have a keto-enol form. [13] Furthermore, barbiturates and thiobarbiturates have some drug significance because they affect the nervous system, [14] have biological evaluations as hypnotic drugs, and have a depressive effect on the central nervous system.…”

Synthesis, characterization and urease inhibitory activities of Zn(II) complexes bearing C1-symmetric ligands derived from (R)-phenylethanamine

“…However, the use of biocompatible metal based-urease inhibitors is much preferred. In recent years, Zn(II) based urease inhibitors play an important role in the treatment of the infections caused by urease producing bacteria Zn(II) complexes [19,20,[26][27][28]. The important fact for targeting Zn(II) system is its biocompatibility and less toxic nature compared to other heavy metals.…”