Urease inhibitors are considered promising compounds for the treatment of ureolytic bacterial infections, particularly infections resulting from Helicobacter pylori in gastric tract. Herein, we present synthesis and inhibitory activity novel highly effective organoselenium as Sporosarcina pasteurii ureases. These studied represent a class competitive reversible urease inhibitors. The most active compound, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen), displayed Ki values equal to 2.11...

A new group of organophosphorus inhibitors urease, P-methyl phosphinic acids was discovered by using the structure based inhibitor design approach. Several derivatives lead compound, aminomethyl(P-methyl)phosphinic acid, were synthesized successfully. Their potency evaluated in vitro against urease from Bacillus pasteurii and Proteus vulgaris. The studied compounds constitute a competitive, reversible bacterial ureases. Obtained thiophosphinic analogues most effective structures exhibited...

In our investigation, we concentrated on naringenin (NG)—a widely studied flavanone that occurs in citrus fruits. As a result of reaction with range alkyl iodides, 7 novel O-alkyl derivatives (7a–11a, 13a, 17a) were obtained. Another chemical modification led to 9 oximes (7b–13b, 16b–17b) never described before. The obtained compounds evaluated for their potential antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. results reported as the standard...

Screening of 25 analogs Ebselen, diversified at the N-aromatic residue, led to identification most potent inhibitors Sporosarcina pasteurii urease reported date. The presence a dihalogenated phenyl ring caused exceptional activity these 1,2-benzisoselenazol-3(2H)-ones, with Ki value in low picomolar range (<20 pM). affinity was attributed increased π–π and π–cation interactions αHis323 αArg339 during initial step binding. Complementary biological studies selected compounds on inhibition...

Urease inhibitors can be considered as a tool to control the damaging effect of ureolytic bacteria infections in humans which occur commonly developed countries. Computer-aided optimization aminomethylphosphinate structures by modifying both their N- and P-termini led invention novel group bacterial ureases. Introduction P-hydroxymethyl into molecule resulted considerable increase inhibitory activity against enzymes purified from Bacillus pasteurii Proteus vulgaris compared with P-methyl...

Key points Relaxin‐3 is a stress‐responsive neuropeptide that acts at its cognate receptor, RXFP3, to alter behaviours including feeding. In this study, we have demonstrated direct, RXFP3‐dependent, inhibitory action of relaxin‐3 on oxytocin and vasopressin paraventricular nucleus (PVN) neuron electrical activity, putative cellular mechanism orexigenic actions relaxin‐3. We observed Gα i/o ‐protein‐dependent influence selective RXFP3 activation PVN neuronal activity in vitro direct neurons,...

Small unextended molecules based on the diamidophosphate structure with a covalent carbon-to-phosphorus bond to improve hydrolytic stability were developed as novel group of inhibitors control microbial urea decomposition. Applying structure-based inhibitor design approach using available crystal structures bacterial urease, N-substituted derivatives aminomethylphosphonic and P-methyl-aminomethylphosphinic acids designed synthesized. In inhibition studies urease from Bacillus pasteurii...

In this study, a new class of bifunctional inhibitors bacterial ureases, important molecular targets for antimicrobial therapies, was developed. The structures the consist combination phosphonate or (2-carboxyethyl)phosphinate functionality with catechol-based fragment, which are designed complexation catalytic nickel ions and covalent bonding thiol group Cys322, respectively. Compounds three types frameworks, including β-3,4-dihydroxyphenyl-, α-3,4-dihydroxybenzyl-,...

A series of 32 thiourea-based urease inhibitors were synthesized and evaluated against native bacterial enzyme whole cells

Catechols have been reported to be potent covalent inhibitors of ureases, and they exhibit activity by modifying cysteine residues at the entrance enzymatic active sites. Following these principles, we designed synthesized novel catecholic derivatives that contained carboxylate phosphonic/phosphinic functionalities assumed expanded specific interactions. When studying chemical stability molecules, found their intrinsic acidity catalyzes spontaneous esterification/hydrolysis reactions in...

Urease is an important virulence factor from Helicobacter pylori that enables bacterial colonization of human gastric mucosa. Specific inhibition urease activity can be regarded as a promising adjuvant strategy for eradication this pathogen. A group organophosphorus inhibitors urease, namely, aminophosphinic acid and aminophosphonic derivatives, were evaluated in vitro against H. urease. The kinetic characteristics recombinant enzyme demonstrated competitive reversible mode with Ki values...

Incorporation of the Beckmann rearrangement into presented research resulted in formation nitrogen-containing terpenoid derivatives originating from naturally occurring compounds. Both starting monoterpenes and obtained were subjected to estimation their antibacterial potential. In study, Staphylococcus aureus was most sensitive examined The Minimal Inhibitory Concentration (MIC) experiments performed on S. demonstrated that (-)-menthone oxime (-)-8 (+)-pulegone (+)-13 had best activity...

The study evaluated the in vitro impact of a series aminophosphinic urease inhibitors on Proteusmirabilis. group compounds comprised structurally diverse analogues diamidophosphate built an N-C-P scaffold. influence inhibition urea-splitting activity was assessed by whole-cell pH-static kinetic measurements. potential to prevent struvite formation determined monitoring changes pH and ionic composition artificial urine medium during P. mirabilis growth. most active exhibited stronger positive...

Condensation of hydroxyalkane-H-phosphinic acids, formaldehyde and secondary amines has given entry to the synthesis variously substituted aminomethane-P-hydroxymethylphosphinic acids.The proposed strategy allowed perform a feasible several molecules with designed biological activity towards bacterial urease -an enzyme which is medicinally relevant molecular target.The inhibitory potency compounds was validated using purified from Bacillus pasteurii.

Candida species, although they are present as commensal organisms in the digestive tract of healthy individuals, can produce a broad spectrum serious illnesses compromised hosts. Fluconazole, water-soluble triazole with bioavailability greater than 90 %, has been extensively used to treat wide range infections. However, growing resistance microorganisms treatment leads discovery new drugs or modifications existing ones. The aim study was investigate whether coordination Cu(II) ions...

The purpose of this work was to examine the effect phosphoric and bisaminophosphinic acids on effectiveness photoinactivation Proteus mirabilis with 5-aminolevulinic acid (5-ALA) as a precursor protoporphyrin IX. Two diode lasers λ = 404 nm (radiation intensity 26 mW cm–2) 630 55 were used sources light. most effective agent (R)-(−)-1,1′-binaphthyl-2,2′-diylhydrogen phosphate, significant improvement in bactericidal 5-ALA-aPDI achieved by pretreating P. compound at nontoxic concentrations...

The phosphinic acid functionality has emerged as an invaluable scaffold for the construction of biologically active compounds, in particular enzyme inhibitors. This article presents two examples recent achievements preparation and application acids ligands hydrolases. Synthetic approaches to a dipeptide analog inhibitor metalloaminopeptidases catechol-based urease are shown. activity mode binding compounds enzymes further discussed.