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• Two Cu(II) complexes of O-N-O Schiff base were synthesized with three different secondary ligands and their urease inhibitory activity was studied. • DFT calculations of three Cu(II) complexes were described. • Their structure-inhibitory activity relationships were discussed. • The 100-ns molecular dynamic (MD) simulations were performed. Two mononuclear Copper(II) complexes, identified as [Cu(C 10 H 8 NO 4 F)(C 6 H 7 N)] (C1) and [Cu(C 10 H 8 NO 4 F)(C 12 H 8 N 2)]·H 2 O·CH 3 OH (C2), incorporating a tridentate Schiff-base ligand with an ONO coordination (C 10 H 8 NO 4 F = 5-fluoro-2-hydroxybenzylidene-L‑serine) and two unique auxiliary ligands (C 6 H 7 N = 4-methylpyridine and C 12 H 8 N 2 = 1,10-phenanthroline) were developed and detailed structurally. Density functional theory (DFT) evaluations of these complexes employed Becke's three-parameter hybrid (B3LYP) approach within the Gaussian 16 computational package. The outcomes from computational analysis corresponded with experimental data. Additionally, the inhibition capabilities of complexes C1 and C2 were evaluated in vitro targeting jack bean urease. Simultaneously, molecular docking was utilized to determine potential binding interactions. Experimental results and docking analyses showed that C1 had considerable inhibitory strength (IC 50 = 2.44 ± 0.15 μM) relative to the benchmark control, acetohydroxamic acid (IC 50 = 27.73 ± 2.93 μM). Furthermore, a 100-ns molecular dynamics assessment was performed to examine the interaction stability of urease with C1 and C2 , using the Desmond 2021 tool from Schrödinger. The correlation between structural configurations and inhibition efficacy was further explored through molecular docking, density functional theory analysis, and molecular dynamics evaluations. [Display omitted] [ABSTRACT FROM AUTHOR]

A new iso-benzofuranone propanamide: 3-(3-oxo-1, 3-dihydroisobenzofuran-1-yl) propanamide (zenkeramide) (1) along with three known compounds: Trans-N-coumaroyltyramine (2), β-Sitosterol (3) and β-sitosterol-3-0-β-D-glucopyranoside (4) were isolated from the ethyl acetate fraction of the stem-bark of Celtis zenkeri Engl (Ulmaceae). The structure of the new compound was elucidated by extensive spectroscopic analysis. The compounds were examined for Urease Inhibitory Activity. Compounds 1 and 2 showed moderate activities (IC50 values (μM) of 42.3 ± 0.19 and 45.2 ± 0.55, respectively), while compounds 3 and 4 were potent inhibitors of the Jack bean urease (IC50 values (μM) of 20.3 ± 0.37and 27.6 ± 0.52, respectively), when compared to the standard inhibitor (thiourea- IC50 21.5 ± 0.47). The isolation of all the compounds from C. zenkeri and the urease activity of compounds 1 and 2 are reported for the first time. [ABSTRACT FROM AUTHOR]

Urease inhibitors can inhibit the decomposition rate of urea, and decrease the air pollution caused by ammonia. In this paper, four new copper(II) complexes [CuL(ONO2)]n (1), [Cu2L2(μ1,3-N3)2] (2), [CuBrL] (3), and [CuClL] (4), where L = 5-bromo-2-(((2-methylamino)ethyl)imino)methyl)phenolate, have been synthesized and characterized. The complexes were characterized by elemental analyses, IR and UV-Vis spectroscopy, molar conductivity, and single crystal X-ray diffraction. X-ray analysis reveals that Cu atoms in complexes 1 and 2 are in square pyramidal coordination, and those in complexes 3 and 4 are in square planar coordination. The molecules of the complexes are linked through hydrogen bonds and π···π interactions. The inhibitory effects of the complexes on Jack bean urease were studied, which showed that the complexes have effective activity on urease.

• Three naphthoquinones di-naphthodiospyrol (A-C) were isolated from Diospyros lotus. • Di-naphthodiospyrol A (1) exhibited 94.2 % urease inhibition activity at 2 µM. • Di-naphthodiospyrol B and C also showed 87.4 and 88.4 % urease inhibition activity at 2 µM. • Diospyros lotus can be utilized for cure of ulcer. Urease is a metallo-protein in which two nickel (Ni) atoms are present at the active site. It is found in all the organisms such as, bacteria, fungi, plants, and in algae. Urease enzymes are also involved in catalyzing the hydrolysis of urea into CO 2 and NH 3. Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. Current research work aimed to purify the three di-naphthodiospyrols namely; 5,4 -dihydroxy-1-methoxy-6,6 -dimethyl7,3-binaphthyl-1,4,5,8-tetraone (1), 5,8 -dihydroxy-5-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4 -tetraone (2) and 8,5,8-trihydroxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4-tetraone (3) from the chloroform fraction of Diospyros lotus roots. The pure constituents (1-3) were evaluated for their urease inhibitory activity. Compounds (1-3) exhibited potent activity with IC 50 value of 28.27 ± 1.68, 20.57 ± 2.00, 27.12 ± 2.45 µ M respectively, when compared with standard thiourea (IC 50 = 21.23 ± 0.12 µ M). The pure isolated compounds (1-3) were also subjected to in silico studies to know their binding pattern with enzyme. The binding orientation and interactions with the important residues of urease enzyme revealed that the three compounds inactivate the enzyme activity by interacting with Ni bi-center as well as with the tailpiece residues. [ABSTRACT FROM AUTHOR]

A new dinuclear copper(II) complex [Cu2(μ-Br)2L2] ⋅ 0.5MeOH with the benzohydrazone ligand 4-bromo-N'-(1-(pyridin-2-yl)ethylidene)benzohydrazide (HL) has been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopic studies. Single crystal structures of the complex and the benzohydrazone compound were studied. The Cu atoms in the complex are coordinated by two benzohydrazone ligands and two Br bridging groups, forming square pyramidal coordination. The complex has good inhibitory activity on Jack bean urease, with IC50 value of1.38 µmol ⋅ L-1. [ABSTRACT FROM AUTHOR]

Reactions of 2-{[5-(Pyridin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid (H2L) with manganese(II), zinc(II) and cadmium(II) acetate in CH3OH/H2O mixture result in the corresponding metal complexes. All the obtained complexes were characterized by IR spectroscopy, elemental analyses, ESI-MS, and single-crystal X-ray diffraction. Structural analyses reveal the dinuclear complexes with the compositions [Mn2L2(CH3OH)2(H2O)2]·2CH3OH (1), [Zn2L2(CH3OH)2(H2O)2]·2CH3OH (2), and 1D chain structure [CdL(H2O)]n (3) in all complexes, H2L is doubly deprotonated (L2-) and serves as equilibrium anion. The carboxylate acts as monodentate ligand in 1 and 2, While μ1,1-bridging ligand in 3. The measurement of Jack Bean urease inhibitory activity showed that 1 and 3 exhibited considerable inhibitory effects for Jack Bean urease with IC50 Values of 12.4 and 2.7 μM, respectively. In addition, bioactive complexes 1 and 3 can effectively bind to bovine serum albumin (BSA), which was assessed by tryptophan emission quenching measurement [ABSTRACT FROM AUTHOR]

A new lactam, oligoamide (1), along with three known compounds (2–4), stigmasterol-3-O-β-D-glucopyranoside (2), formononetin (3) and (-)-pinitol (4) were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Angylocalyx oligophyllus by chromatographic separation. Their structures were elucidated on the basis of spectroscopic analysis (UV, IR, MS, 1D, and 2D NMR). Compound 1 was found to have weak antioxidant and urease inhibitory potential. [ABSTRACT FROM AUTHOR]

A series of new ZnII, CoII/III and NiII complexes derived from reduced Schiff base were prepared and characterized. The cobalt complex and the nickel complex have effective urease inhibitory activities. Molecular docking study of the complexes was studied. A series of new ZnII, CoII/III and NiII complexes derived from reduced Schiff base 6,6′-((propane-1,3-diylbis(azanediyl))bis(methylene))bis(2-ethoxyphenol) (H 2 L), [Zn 3 L 2 (N 3) 2 ] (1), [Co 2 L(N 3) 2 (CH 3 COO)]·CH 3 OH (2) and [Ni(HL)(OH 2)(CH 3 OH)]·ClO 4 (3), were prepared and characterized by physico-chemical methods. Crystal structures of the complexes were determined by single crystal X-ray diffraction. Complex 1 is a trinuclear zinc(II) compound. Complex 2 is a dinuclear cobalt(II/III) compound. Complex 3 is a mononuclear nickel(II) compound. The cobalt complex and the nickel complex have effective urease inhibitory activities, with IC 50 values of 19.8 and 11.6 μmol·L−1, respectively. However, the zinc complex 1 has no such activity. Molecular docking study of complexes 2 and 3 with the active center of Jack bean urease was studied. [ABSTRACT FROM AUTHOR]

Highlights • Pancreatic hydrolysis improves the biological properties of camel milk αS-casein. • Camel milk αS-casein and its hydrolysate fractions inhibit oxidation reactions and enzymatic inhibitory activities. • Camel αS-casein is a source of multifunctional peptides. Abstract The aim of this study was to investigate the effect of pancreatic enzymes hydrolysis of camel αS-casein on their antioxidant, tyrosinase and urease inhibitory activities. Isolated αS-casein was hydrolyzed, fractionated and assayed for their antioxidant properties by using four complementary tests; namely, ABTS•+ scavenging, hydroxyl radical scavenging, ferrous ion chelating and β-carotene-linoleic acid assays. The in vitro enzymatic inhibitory activity was determined by using L-DOPA as a substrate and indophenol method for tyrosinase and urease inhibitory activity, respectively. After enzymatic hydrolysis, the activities were significantly increased whereas chymotryptic hydrolysis released peptides with higher activity than trypsin. The obtained fraction with low molecular weight (<10 kDa) exhibited the highest antioxidant and enzymatic inhibitory activities. Results suggested that antioxidant properties of peptides affect their tyrosinase inhibitory activity. This study reveals that camel milk αS-casein is as a great candidate for incorporation into functional foods to help in preventing disorders caused by oxidative reactions in food and human body's. [ABSTRACT FROM AUTHOR]

In the current study, a series of 3,4-dihydro-2-pyridone derivatives were synthesized in a one-pot four- component reaction of Meldrum's acid, benzaldehyde derivatives, methyl acetoacetate, and ammonium acetate. SiO2-Pr-SO3H was used as an efficient catalyst for the synthesis of the target compounds under solvent-free conditions. The most probable mechanism for this reaction has been discussed. The advantages of this methodology are high product yields, being environmentally benign, short reaction times, and easy handling. Eight 2-pyridinone derivatives were evaluated for their inhibitory activities against Jack bean urease. Molecular docking study of the synthesized compounds was also evaluated. All compounds showed good activities against urease and among them, 4-(4-nitrophenyl)-5-methoxycarbonyl-6-methyl-3,4- dihydropyridone (5a) showed the most potent activity (IC50 = 29.12 µM), more potent than hydroxyurea as the reference drug (IC50 = 100.0 µM). Also, the results from docking studies were in good agreement with those obtained with in vitro assay. According to the docking studies methionine (Met) 637 and nitro phenyl ring cause n-π interaction between lone pair of sulfur atom and π aromatic ring. Moreover, hydrophobic interactions existed between compound 5a and alanine (ALA) 636, ALA 440, and isoleucine 411. The results indicated that the inhibitory activities increased with the increase of electron withdrawing ability of the groups despite a less important role of lipophilicity in increasing the inhibitory activity.

Graphical abstract Highlights • Synthesis of urea and thiourea derivatives of tryptamine. • Urease inhibitory activity of synthesized derivatives have been evaluated. • Kinetic study of the compounds (1 – 25) has been performed. • The in silico study of the active compounds was also done. Abstract Urease is an enzyme of amidohydrolase family and is responsible for the different pathological conditions in the human body including peptic ulcers, catheter encrustation, kidney stone formation, hepatic coma, encephalopathy, and many others. Therefore, the search for potent urease inhibitors has attracted major scientific attention in recent years. Urea and thiourea derivatives of tryptamine (1 – 25) were synthesized via reaction of tryptamine with different substituted phenyl isocyanates/isothiocyanates. The synthetic compounds were evaluated for their urease enzyme inhibitory activity and they exhibited good inhibitory potential against urease enzyme in the range of (IC 50 = 11.4 ± 0.4–24.2 ± 1.5 μM) as compared to the standard thiourea (IC 50 = 21.2 ± 1.3 μM). Out of twenty-five compounds, fourteen were found to be more active than the standard. Limited structure-activity relationship suggested that the compounds with CH 3 , and OCH 3 substituents at aryl part were the most potent derivatives. Compound 14 (IC 50 = 11.4 ± 0.4 μM) with a methyl substituent at ortho position was found to be the most active member of the series. Whereas, among halogen substituted derivatives, para substituted chloro compound 16 (IC 50 = 13.7 ± 0.9 μM) showed good urease inhibitory activity. These synthetic derivatives were found to be non-cytotoxic in cellular assay. Kinetic studies revealed that the compounds 11 , 12 , 14 , 17 , 21 , 22 , and 24 showed a non-competitive type of inhibition. In silico study identified the possible bindings interactions of potential inhibitors with the active site of enzyme. These newly identified inhibitors of urease enzyme can serve as leads for further research and development. [ABSTRACT FROM AUTHOR]

Abstract The current study was designed to evaluate the urease inhibitory activities of the fractions of Ferula narthex Bioss, followed by bioassay guided isolation of new urease sesquiterpene coumarins, as potential urease inhibitors. The chloroform and ethylacetate fractions were found to be active against urease enzyme with IC 50 values of 42.5 and 169.3 μg/mL, respectively. Activity-directed fractionation and purification of chloroform fraction lead to the isolation of compounds 2 – 5. , whereas compound 1 was isolated from ethylacetate faction. The compounds 5 showed a moderate urease inhibition with IC 50 value of 18.80 μg/mL, followed by compound 2 and 3 having IC 50 values of 148.94 and 177.59 μg/mL, respectively. The binding mode of interaction and energy of these compounds 2 , 3 and 5 in the active site of urease were also identified by molecular docking studies. In summary, the extract showed good urease inhibition and their isolated compounds showed moderate to weak inhibition. Highlights • Bioassay guided isolation of sesquiterpene coumarins from Ferula narthex Bioss • The chloroform and ethylacetate fractions showed good urease inhibition activities. • Compounds 1 and 2 – 5 were isolated from ethylacetate and chloroform fractions respectively. • Compounds 2 , 3 and 5 demonstrated moderate urease inhibition with IC 50 values in range of 18.80–177.59 ± 2.10 μg/mL. • Molecular docking studies of compounds 2 , 3 and 5 were carried out. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Benzylidine indane-1,3-diones (1–30) were synthesized. • Structures of all compounds were confirmed by various spectroscopic techniques. • All compounds were evaluated for in vitro urease inhibitory activity. • Limited structure-activity relationship was established. • In silico study was performed on active analogs. Abstract Current study deals with the evaluation of indane-1,3-dione based compounds as new class of urease inhibitors. For that purpose, benzylidine indane-1,3-diones (1 – 30) were synthesized and fully characterized by different spectroscopic techniques including EI-MS, HREI-MS, 1H, and 13C NMR. All synthetic molecules 1 – 30 were evaluated for urease inhibitory activity and showed good to moderate inhibitory potential within the range of (IC 50 = 11.60 ± 0.3–257.05 ± 0.7 µM) as compared to the standard acetohydroxamic acid (IC 50 = 27.0 ± 0.5 µM). Compound 1 (IC 50 = 11.60 ± 0.3 µM) was found to be most potent inhibitor amongst all derivatives. The key binding interactions of most active compounds within the enzyme pocket were evaluated through in silico studies. [ABSTRACT FROM AUTHOR]

A series of 1-[(4′-chlorophenyl)carbonyl-4-(aryl)thiosemicarbazide derivatives 1 – 25 was synthesized and characterized by spectroscopic techniques such as EI-MS and 1 H NMR. All compounds were screened for urease inhibitory activity in vitro and demonstrated excellent inhibitory activity in the range of IC 50  = 0.32 ± 0.01–25.13 ± 0.13 μM as compared to the standard thiourea (IC 50  = 21.25 ± 0.13 μM). Amongst the potent analogs, compounds 3 (IC 50  = 2.31 ± 0.01 μM), 6 (IC 50  = 2.14 ± 0.04 μM), 10 (IC 50  = 1.14 ± 0.06 μM), 20 (IC 50  = 2.15 ± 0.05 μM), and 25 (IC 50  = 0.32 ± 0.01 μM) are many folds more active than the standard. Structure-activity relationship (SAR) was rationalized by looking at the effect of diversely substituted aryl ring on inhibitory potential which predicted that regardless of the nature of substituents, their positions on aryl ring is worth important for the potent activity. Furthermore, to verify these interpretations, in silico study was performed on all compounds and a good correlation was perceived between the biological evaluation and docking study of compounds. [ABSTRACT FROM AUTHOR]

Benzimidazole derivatives exhibited a broad range of biological activities, e.g., antimicrobial, antiviral, anthelmintic, anti-inflammatory, anticancer and as an anti-ulcer/proton pump inhibitor. Keeping in view the large number of reported drugs containing benzimidazole moiety on one hand and sulfonamide on the other hand, a small series of N-tosyl benzimidazoles (4a-e) have been synthesized. The present work describes the synthesis, characterization and bioevaluation of five new N-tosyl benzimidazoles with the objective to develop new compounds with improved anticancer, antibacterial and urease inhibitory activities. The substituted 1,2- phenylenediamines in the first step were condensed with aliphatic carboxylic acids to synthesize the substituted benzimidazoles. In the second step the tosyl chloride was reacted with substituted benzimidazoles in basic conditions to afford the title N-tosyl benzimidazoles (4a-e). The screening for their antitumor activities was performed against Agrobacterium tumefaciens by following the potato disc tumor assay. The compound (4e) exhibited excellent antitumor activity with IC50 values 474.45μgml-1 compared to other synthesized compounds. Antibacterial activity results revealed that compounds 4d and 4e having methyl and ethyl substitution respectively at the imidazole ring showed excellent zone inhibition against both gram positive and gram negative strains. The urease inhibitory activity results showed that derivative 4e exhibited highest potential to inhibit the urease enzyme compared to all other derivatives. Based upon our investigation it is proposed that compound (4e) may serve as lead structure to design more potent biological active compounds having multitargets inhibition activities [ABSTRACT FROM AUTHOR]

In the current study, a series of 3,4-dihydro-2-pyridone derivatives were synthesized in a one-pot four- component reaction of Meldrum's acid, benzaldehyde derivatives, methyl acetoacetate, and ammonium acetate. SiO2-Pr-SO3H was used as an efficient catalyst for the synthesis of the target compounds under solvent-free conditions. The most probable mechanism for this reaction has been discussed. The advantages of this methodology are high product yields, being environmentally benign, short reaction times, and easy handling. Eight 2-pyridinone derivatives were evaluated for their inhibitory activities against Jack bean urease. Molecular docking study of the synthesized compounds was also evaluated. All compounds showed good activities against urease and among them, 4-(4-nitrophenyl)-5-methoxycarbonyl-6-methyl-3,4- dihydropyridone (5a) showed the most potent activity (IC50 = 29.12 µM), more potent than hydroxyurea as the reference drug (IC50 = 100.0 µM). Also, the results from docking studies were in good agreement with those obtained with in vitro assay. According to the docking studies methionine (Met) 637 and nitro phenyl ring cause n-π interaction between lone pair of sulfur atom and π aromatic ring. Moreover, hydrophobic interactions existed between compound 5a and alanine (ALA) 636, ALA 440, and isoleucine 411. The results indicated that the inhibitory activities increased with the increase of electron withdrawing ability of the groups despite a less important role of lipophilicity in increasing the inhibitory activity. [ABSTRACT FROM AUTHOR]

The dimeric napthoquione 5,8,4′-trihydroxy-1′-methoxy-6, 6′-dimethyl-7,3′-binaphtyl-1,4,5′,8′-tetraone (1) was isolated from the chloroform fraction ofDiospyros lotusextract.Compound1was screened for its inhibitory effects against four enzymes: urease, phosphodiesterase-I, carbonic anhydrase-II andα-chymotrypsin, and showed selective activity against urease enzyme with an IC50value of 254.1 ± 3.82 μM as compared to the standard thiourea (IC50 = 21 ± 0.11 μM). Furthermore,in silicodocking study was carried out to explain the molecular mechanism of compound1against the target receptor. [ABSTRACT FROM PUBLISHER]

Different parts of Acacia nilotica (L.) Delile, Calotropis procera (Aiton) W.T. Aiton, Adhatoda vasica Nees, Fagoniaar abica L. and Casuarina equisetifolia L. are traditionally used in folk medicine for the treatment of a variety of common ailments like nausea, cold, cough, asthma, fevers, diarrhea, sore throat, swelling, etc. The present study was aimed to evaluate the anti-Helicobacter pylori and urease inhibition activities of extracts produced from the above selected medicinal plants native to Soon Valley (home to an old civilization) in the Punjab province of Pakistan. Methanol, acetone and water extracts of the plants were evaluated for anti-bacterial activity against thirty four clinical isolates and two reference strains of H. pylori. Minimum inhibitory concentrations (MICs) of the extracts were determined using the agar dilution method and compared with some standard antibiotics like amoxicillin (AMX), clarithromycin (CLA), tetracycline (TET) and metronidazole (MNZ), used in the triple therapy for H. pylori eradication. H. pylori urease inhibition activity of the extracts was assessed by the phenol red method, wherein, Lineweaver-Burk plots were used to determine Michaelis-Menten constants for elucidating the mechanism of inhibition. Methanol and acetone extracts from Acacia nilotica and Calotropis procera exhibited stronger anti-H. pylori activity than MNZ, almost comparable activity with TET, but were found to be less potent than AMX and CLT. The rest of the extracts exhibited lower activity than the standard antibiotics used in this study. In the H. pylori urease inhibitory assay, methanol and acetone extracts of Acacia nilotica and Calotropis procera showed significant inhibition. Lineweaver-Burk plots indicated a competitive mechanism for extract of Acacia nilotica, whereas extract of Calotropis procera exhibited a mixed type of inhibition.

The current study was designed to evaluate the urease inhibitory profile of extract and fractions ofPistacia atlanticassp. cabulica Stocks followed by bioactivity-guided isolated compounds. The crude extract was found significantly active with urease inhibitor (95.40% at 0.2 mg/mL) with IC50values of 32.0 ± 0.28 μg/mL. Upon fractionation, ethyl acetate fraction displayed 100% urease inhibition with IC50values of 19.9 ± 0.51 μg/mL at 0.2 mg/mL. However,n-hexane and chloroform fractions exhibited insignificant urease inhibition. Similarly, the isolated compound, transilitin (1) and dihydro luteolin (2) demonstrated marked urease attenuation with 95 and 98% respectively, at 0.15 mg/mL. Both the isolated compounds showed marked potency with IC50values of 8.54 ± 0.54 and 9.58 ± 2.22 μg/mL, respectively. In short, both the extract and fractions and isolated compounds showed marked urease inhibition and thus a useful natural source of urease inhibition. Graphical abstract showing the imagePistacia atlantica, chemical structure of isolated compounds and urease enzyme. [ABSTRACT FROM PUBLISHER]

The in vitro urease inhibitory activity of fixed oil and various organic fractions of Caralluma tuberculata followed by GC-MS analysis of the fixed oil are described in this research article. The fixed oil caused marked attenuation of jack bean urease with half-maximal inhibitory concentration (IC50) of 2.97 mg/ml. The similar urease inhibitory profile was observed for chloroform and ethyl acetate fractions with IC50 values of 3.36 and 4.90 mg/ml, respectively. GC-MS analysis led to the identification of 20 different constituents of the fixed oil by their m/z ratio and retention time in comparison with the standard compounds. The major constituents were methyl linoleate (30.97%) followed by methyl octadecadienoate (19.16%), ethyl linolenate (13.70 %), and methyl palmitate (9.86 %). The fixed oil and organic fractions of C. tuberculata exhibited marked urease inhibition and thus provide scientific background for use of the plant as antiulcer agent. [ABSTRACT FROM AUTHOR]

A simple and practical method is described for the synthesis of novel 5-arylidene derivatives of barbituric and thiobarbituric acid. 2-Formylbenzoic acids reacted easily with (thio)barbituric acids in the presence of p-toluenesulfonic acid ( p-TsOH) in MeOH/EtOH to obtain the title compound in good yields. Then, their urease inhibitory activity were evaluated in vitro and compared with hydroxyurea as the reference drug. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Five ursane type sulfated saponins have been isolated from the aerial parts of Zygophyllum fabago Linn. (locally called Chashum). The urease inhibitory effects of these compounds have been investigated for the first time as well as their molecular docking studies have also been carried out to check the structure–activity relationship. The IC50 values of these compounds could not be found due to paucity of the samples. The molecular docking studies were performed only for the most active compound mono sodium salt of 3β,23-di-O-sulfonyl-23-hydroxyurs-20(21)-en-28-oic acid 28-O-[β-d-glucopyranosyl] ester (Zygofaboside A; 1). [Copyright &y& Elsevier]

Different parts of Acacia nilotica (L.) Delile, Calotropis procera (Aiton) W.T. Aiton, Adhatoda vasica Nees, Fagoniaar abica L. and Casuarina equisetifolia L. are traditionally used in folk medicine for the treatment of a variety of common ailments like nausea, cold, cough, asthma, fevers, diarrhea, sore throat, swelling, etc. The present study was aimed to evaluate the anti-Helicobacter pylori and urease inhibition activities of extracts produced from the above selected medicinal plants native to Soon Valley (home to an old civilization) in the Punjab province of Pakistan. Methanol, acetone and water extracts of the plants were evaluated for anti-bacterial activity against thirty four clinical isolates and two reference strains of H. pylori. Minimum inhibitory concentrations (MICs) of the extracts were determined using the agar dilution method and compared with some standard antibiotics like amoxicillin (AMX), clarithromycin (CLA), tetracycline (TET) and metronidazole (MNZ), used in the triple therapy for H. pylori eradication. H. pylori urease inhibition activity of the extracts was assessed by the phenol red method, wherein, Lineweaver-Burk plots were used to determine Michaelis-Menten constants for elucidating the mechanism of inhibition. Methanol and acetone extracts from Acacia nilotica and Calotropis procera exhibited stronger anti-H. pylori activity than MNZ, almost comparable activity with TET, but were found to be less potent than AMX and CLT. The rest of the extracts exhibited lower activity than the standard antibiotics used in this study. In the H. pylori urease inhibitory assay, methanol and acetone extracts of Acacia nilotica and Calotropis procera showed significant inhibition. Lineweaver-Burk plots indicated a competitive mechanism for extract of Acacia nilotica, whereas extract of Calotropis procera exhibited a mixed type of inhibition. [ABSTRACT FROM AUTHOR]

Two isostructural cadmium(II) complexes, [Cd(L1)(NO3)2 (H2O)] · CH3OH (1) and [Cd(L2)(NO3)2(H2O)] · CH3OH (2), derived from the Schiff bases 4-bromo-2-[(2-piperazinylethylimino)methyl]phenol (L1) and 4-chloro-2-[(2-piperazinylethylimino)methyl]phenol (L2), respectively, were prepared and structurally characterized by X-ray diffraction. Each complex consists of a mononuclear cadmium(II) complex molecule and a methanol molecule of crystallization. The Cd atom in each complex is six-coordinated by one phenolate O, one imine N and one amine N atoms of the Schiff base ligand, two O atoms from two nitrate anions, and one water O atom, forming distorted octahedral coordination. The urease inhibitory activities of the complexes were evaluated. [ABSTRACT FROM AUTHOR]

Two new copper(II) complexes, [CuBrL1] (1) and [CuBrL2] (2) (HL1 = 1-[(2-diethylaminoethylimino)methyl] naphthalen-2ol, HL2 = 2,4-dibromo-6-[(2-diethylaminoethy limino) methyl]phenol), were prepared and structurally characterized by elemental analyses, infrared spectroscopy, and single-crystal X-ray diffraction. Both complexes are mononuclear copper(II) compounds. The Cu atom in each of the complexes is four-coordinate in a square planar geometry. Both complexes show potent urease inhibitory activities. [ABSTRACT FROM AUTHOR]

Summary: This piece of work has been planned to investigate pharmacochemically the young stems of Alstonia scholaris. Chromatographic resolution on the methanolic extract provided platanic acid (1), stigmastan-4-en-3-one (2), coniferyl aldehyde (3), 2,6-dimethoxyquinone (4) and 7-hydroxycoumarine (5) which have not been reported so far from the genus Alstonia. The other obtained metabolites include: β-Amyrin (6), lupeol (7), β-sitosterol-3-O-β-D-glucopyranoside (8), cycloeucalenol (9), betulinic acid (10), lupeol acetate (11), loganin (12), 19, 20-Z-vallesamine (13), echitamine (14) and normavacurine-21-one (15) have also been isolated and characterized. Biological screening of the crude methanolic extract revealed potent antioxidant and urease inhibitory activities. Among the isolates, 19, 20-Z-vallesamine and loganin showed potent antioxidant activity while significant antioxidant potential was observed for coniferyl aldehyde. On the other hand, compounds 1, 7, 8 and 11 revealed significant urease inhibitory potential while 2, 4 and 12 were moderately active. Significant xanthine oxidase activity was also observed for 3 and 12. [ABSTRACT FROM AUTHOR]

• Synthesis of 4-oxycoumarinyl linked acetohydrazide Schiff bases 3 – 27. • Characterization of all analogs by various spectroscopic techniques. • Urease inhibitory activity in vitro. • Structure-activity relationship (SAR). • Molecular docking studies to rationalize the binding interactions. Urease enzyme is responsible to catalyze the hydrolysis of urea into carbamate and ammonia. Then carbamate hydrolyzed to ammonia and carbon dioxide. Excess release of ammonia leads to increase pH in stomach that actually encourages the survival of Helicobacter pylori. H. pylori involves in various disorders most commonly peptic ulcer, pyelonephritis, hepatic coma, kidney stone formation, urolithiasis, and encephalopathy. Apart from many pharmacological properties, coumarin and Schiff bases are known to possess urease inhibitory activity. Therefore, these two pharmacologically important scaffolds are combined into single hybrid molecules to assess their potential as urease inhibitors. For this aim, N ′-benzylidene-2-((2-oxo-2 H -chromen-4-yl)oxy)acetohydrazide Schiff base derivatives 3 – 27 were synthesized by following a three step reaction strategy. Structures of all synthetic molecules were characterized by EI-MS, 1H-, and 13C NMR spectroscopic techniques. All molecules were assessed for urease inhibitory activity and found to possess a varying degree of inhibitory potential in the range of IC 50 = 12.3 ± 0.69 to 88.8 ± 0.04 μM. Amongst the active analogs, compounds 7 (IC 50 = 16.2 ± 0.11 μM), 9 (IC 50 = 15.2 ± 0.14 μM), 10 (IC 50 = 12.3 ± 0.69 μM), 12 (IC 50 = 16.3 ± 0.45 μM), and 15 (IC 50 = 17.6 ± 0.28 μM) were identified as potent inhibitors compared to standard urea (IC 50 = 21.5 ± 0.47 μM). It is conferred from structure-activity relationship (SAR) that variation in inhibitory activity is due to different substitutions pattern on aryl ring. Moreover, molecular docking studies were carried out to understand the interactions of ligand with the active pocket of urease enzyme. [ABSTRACT FROM AUTHOR]

The current project reports the synthesis and characterization of a previously known Schiff base compound, 4-bromo-2-(((2′-chloro-4′-nitrophenyl)imino)methyl)phenol (SBA), through the condensation reaction of 2-chloro-4-nitroaniline and 5-bromo-2-hydroxybenzaldehyde, in a solvent-free mechanochemical green grinding method. It was obtained as bright red crystals. Its structure was elucidated based on XRD (X-Ray Diffraction) and IR, MS and NMR spectroscopy. The crystal structure was found to be monoclinic. Hirshfeld surfaces analysis has also been conducted to elucidate the intermolecular interactions. The base showed considerable urease inhibitory activity with IC 50 (μg/mL) 30.65 as compared to 11.14 of the standard thiourea. The compound showed minimal free radical scavenging activity (EC 50 (μg/mL) 1127). In conclusion, grinding is a viable method for the synthesis of this Schiff base. It can find its application as a potential urease inhibitor in the field of medicine and agriculture. • Synthesis of Schiff base 4-bromo-2-(((2′-chloro-4′-nitrophenyl)imino)methyl)phenol. • Green and efficient solvent-free mechanochemical grinding method. • Crystal structure by XRD (X-Ray Diffraction). • Hirshfeld surfaces analysis. • Urease inhibitory activity of the base to find its use in medicine and agriculture. [ABSTRACT FROM AUTHOR]