thiourea and thiobarbituric-acid

A new series of 1,2,3-triazole-(thio)barbituric acid hybrids 8a-n was designed and synthesized on the basis of potent pharmacophores with urease inhibitory activity. Therefore, these compounds were evaluated against Helicobacter pylori urease. The obtained result demonstrated that all the synthesized compounds, 8a-n, were more potent than the standard urease inhibitor, hydroxyurea. Moreover, among them, compounds 8a, 8c-e, 8g,h, and 8k,l exhibited higher urease inhibitory activities than the other standard inhibitor used: thiourea. Docking studies were performed with the synthesized compounds. Furthermore, molecular dynamic simulation of the most potent compounds, 8e and 8l, showed that these compounds interacted with the conserved residues Cys592 and His593, which belong to the active site flap and are essential for enzymatic activity. These interactions have two consequences: (a) blocking the movement of a flap at the entrance of the active site channel and (b) stabilizing the closed active site flap conformation, which significantly reduces the catalytic activity of urease. Calculation of the physicochemical and topological properties of the synthesized compounds 8a-n predicted that all these compounds can be orally active. The ADME prediction of compounds 8a-n was also performed.

Topics: Anti-Bacterial Agents; Enzyme Inhibitors; Helicobacter pylori; Molecular Docking Simulation; Molecular Dynamics Simulation; Structure-Activity Relationship; Thiobarbiturates; Thiourea; Triazoles; Urease

In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1-9 and 19-27) were found to exhibit low to moderate activity however thiobarbituric acid derived compounds (10-18 and 28-36) showed significant inhibition activity at low micro-molar concentrations. Among the synthesized compounds, compounds (15), (12), (10), (36), (16) and (35) showed excellent urease inhibition with IC50 values 8.53 ± 0.027, 8.93 ± 0.027, 12.96 ± 0.13, 15 ± 0.098, 18.9 ± 0.027 and 19.7 ± 0.63 μM, respectively, even better than the reference compound thiourea (IC50 = 21 ± 0.011). The compound (11) exhibited comparable activity to the standard with IC50 value 21.83 ± 0.19 μM. In silico molecular docking studies for most active compounds (10), (12), (15), (16), (35) and (36) and two inactive compounds (3) and (6) were performed to predict the binding patterns.

Topics: Computer Simulation; Enzyme Inhibitors; Models, Molecular; Structure-Activity Relationship; Thiobarbiturates; Urease

A series of thiobarbituric acid derivatives 1-27 were synthesized and evaluated for their urease inhibitory potential. Exciting results were obtained from the screening of these compounds 1-27. Compounds 5, 7, 8, 11, 16, 17, 22, 23 and 24 showed excellent urease inhibition with IC50 values 18.1 ± 0.52, 16.0 ± 0.45, 16.0 ± 0.22, 14.3 ± 0.27, 6.7 ± 0.27, 10.6 ± 0.17, 19.2 ± 0.29, 18.2 ± 0.76 and 1.61 ± 0.18 μM, respectively, much better than the standard urease inhibitor thiourea (IC₅₀=21 ± 0.11 μM). Compound 3, 4, 10, and 26 exhibited comparable activities to the standard with IC₅₀ values 21.4 ± 1.04 and 21.5 ± 0.61 μM, 22.8 ± 0.32, 25.2 ± 0.63, respectively. However the remaining compounds also showed prominent inhibitory potential The structure-activity relationship was established for these compounds. This study identified a novel class of urease inhibitors. The structures of all compounds were confirmed through spectroscopic techniques such as EI-MS and (1)H NMR.

Topics: Enzyme Inhibitors; Kinetics; Protein Binding; Structure-Activity Relationship; Thiobarbiturates; Urease

Cytotoxic effects of catecholamine are thought to be caused by the formation of 0-semiquinone and superoxide radicals. Dopamine in the presence of copper ions releases aldehydic products from glutamate, deoxyuridine or DNA capable of reacting with 2-thiobarbituric acid (TBA). The formation of TBA reactive products (TBAR) was concentration dependent of both dopamine and copper ion. Complete inhibition of formation of TBAR from glutamate, deoxyuridine or DNA was observed in the presence of thiourea and catalase. Mannitol, albumin and superoxide dismutase offered substantial protection. The present data indicate that dopamine in the presence of copper ions can lead to the formation of reactive hydroxyl radicals which can release aldehydic products from glutamate, deoxyuridine or DNA capable of reacting with TBA.

Topics: Aldehydes; Animals; Catalase; Copper; Deoxyuridine; DNA; Dopamine; Glutamates; Glutamic Acid; Oxidation-Reduction; Thiobarbiturates; Thiourea

The authors have examined the possibility of replacing sodium arsenite with acetyl thiourea and of using butanol acidified with phosphoric acid in measuring sialic acids in biologic material. The results evidence a sufficient specificity, reproducibility, higher sensitivity and lower toxicity of the modification as compared to the routine technique, for this modification does not involve the use of highly toxic sodium arsenite and of highly volatile aggressive butanol/hydrochloric acid mixture.

Topics: Arsenic; Arsenites; Humans; Indicators and Reagents; N-Acetylneuraminic Acid; Sialic Acids; Sodium Compounds; Thiobarbiturates; Thiourea

Cytotoxic effects of various quinone compounds are thought to be due to the formation of semiquinone free radicals. Hydroquinone and 1,2,4-benzenetriol in the presence of copper ions release from glutamate or DNA aldehydic products capable of reacting with 2-thiobarbituric acid (TBA). The formation of TBA reactive products (TBAR) was greater in the presence of 1,2,4-benzenetriol in comparison with hydroquinone. Complete inhibition of formation of TBAR from glutamate by 1,2,4-benzenetriol and copper was observed in the presence of catalase, thiourea and mannitol. Albumin and superoxide dismutase offered substantial protection. Complete protection of formation of TBAR from DNA was observed in the presence of catalase and thiourea. Presence of albumin, mannitol and superoxide dismutase caused only partial inhibition. The formation of TBAR from glutamate or DNA is dependent on copper ion concentration. The present data indicate that hydroquinone and 1,2,4-benzenetriol in the presence of copper ions can lead to the formation of reactive hydroxyl radicals which can release TBAR from glutamate or DNA.

Topics: Albumins; Animals; Catalase; Cattle; Copper; DNA; DNA Damage; Drug Synergism; Free Radicals; Glutamates; Glutamic Acid; Hydroquinones; In Vitro Techniques; Mannitol; Superoxide Dismutase; Thiobarbiturates; Thiourea

Topics: Anesthesia, Local; Anesthetics; Anesthetics, Local; Barbiturates; Thiobarbiturates; Thiourea

Topics: Anti-Bacterial Agents; Barbiturates; Methylthiouracil; Polarography; Thiobarbiturates; Thiouracil; Thiourea; Urea

Topics: Antithyroid Agents; Barbital; Methylthiouracil; Thiazoles; Thiobarbiturates; Thiopental; Thiourea; Thyroid Gland