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1.
Various inhibitors were tested for their inhibitory effects on soybean urease. The Ki values for boric acid, 4-bromophenylboronic acid, butylboronic acid, and phenylboronic acid were 0.20?±?0.05?mM, 0.22?±?0.04?mM, 1.50?±?0.10?mM, and 2.00?±?0.11?mM, respectively. The inhibition was competitive type with boric acid and boronic acids. Heavy metal ions including Ag+, Hg2+, and Cu2+ showed strong inhibition on soybean urease, with the silver ion being a potent inhibitor (IC50 = 2.3?×?10?8 mM). Time-dependent inhibition studies exhibited biphasic kinetics with all heavy metal ions. Furthermore, inhibition studies with sodium salts of mineral acids (NaF, NaCl, NaNO3, and Na2SO4) showed that only F? inhibited soybean urease significantly (IC50 = 2.9?mM). Competitive type of inhibition was observed for this anion with a Ki value of 1.30?mM.  相似文献   

2.
Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14?±?0.01 to 18.50?±?0.90?μM when compared with the standard inhibitor thiourea having IC50 value 21.25?±?0.90?μM. Among the series, analog 9 (0.14?±?0.01?μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.  相似文献   

3.
4-(3-(4-Substituted-phenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamides (9–16) were successfully synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectra. Carbonic anhydrase I and II inhibitory effects of the compounds were investigated. Ki values of the compounds were in the range of 316.7?±?9.6–533.1?±?187.8?nM towards hCA I and 412.5?±?115.4–624.6?±?168.2?nM towards hCA II isoenzymes. While Ki values of the reference compound Acetazolamide were 278.8?±?44.3?nM and 293.4?±?46.4?nM towards hCA I and hCA II izoenzymes, respectively. Compound 14 with bromine and compound 13 with fluorine substituents can be considered as the leader compounds of the series because of the lowest Ki values in series to make further detailed carbonic anhydrase inhibiton studies.  相似文献   

4.
The M2 isoform of pyruvate kinase (PKM2) is a potential antitumor therapeutic target. In this study, we designed and synthesised a series of 2, 3-didithiocarbamate substituted naphthoquinones as PKM2 inhibitors based on the lead compound 3k that we previously reported. Among them, compound 3f (IC50?=?1.05?±?0.17 µM) and 3h (IC50?=?0.96?±?0.18 µM) exhibited potent inhibition of PKM2, and their inhibitory activities are superior to compound 3k (IC50?=?2.95?±?0.53 µM) and the known PKM2 inhibitor shikonin (IC50?=?8.82?±?2.62 µM). In addition, we evaluated in vitro antiproliferative effects of target compounds using MTS assay. Most target compounds exhibited dose-dependent cytotoxicity with IC50 values in nanomolar concentrations against HCT116, MCF7, Hela, H1299 and B16 cells. These small molecule PKM2 inhibitors not only provide candidate compounds for cancer therapy, but also offer a tool to probe the biological effects of PKM2 inhibition on cancer cells.  相似文献   

5.
6.
Some new structural type inhibitors of urease, i.e. 2,5-disubstituted-1,3,4-oxadiazoles (4a–e) and 4,5-disubstituted-1,2,4-triazole-3-thiones (5a–e) were synthesized in two steps from mandelic acid hydrazides (2a–e) and aryl isothiocyantes. The hydrazides in turn were synthesized from mandelic acid via esterification. Compounds 4a–e and 5a–e were evaluated against jack bean urease. Compounds 4d, 5b, and 5d were found to be more potent, with IC50 values of 16.1?±?0.12?µM, 18.9?±?0.188?µM, and 16.7?±?0.178?µM, respectively, when compared to the standard (thiourea; IC50?=?21.0?±?0.011?µM). These compounds may be subjected to further investigations for the development of antiulcer drugs.  相似文献   

7.
Gaeolaelaps aculeifer (Canestrini, 1883) is a soil-dwelling predatory mite with potential for use as a biological control agent of fungus gnats (Diptera: Sciaridae) in mushroom production. The life table, predation rate and population growth rate of G. aculeifer on a diet of larvae of the sciarid fly, Lycoriella auripila, at 23?±?1°C, 60?±?5% RH and a photoperiod of 0:24 (L:D)?h was investigated. The results revealed that the duration of egg, larva, protonymph, deutonymph, females and males of G. aculeifer were 3.8?±?0.1, 1.4?±?0.1, 3.9?±?0.1, 4.1?±?0.1, 67.7?±?2.8 and 60.3?±?3.1 days, respectively. Net reproductive rate (R0) was 54.8?±?7.1 offspring, intrinsic rate of increase (r) was 0.12?±?0.01 offspring day?1, finite rate of increase (λ) was 1.13?±?0.01 day?1and mean generation time (T) was 32.3?±?0.6 days. The predator consumed a mean of 0.08?±?0.05, 1.73?±?0.18, 3.16?±?0.28 and 75.9?±?7.1 third instar L. auripila larvae during the larval (1.3?±?0.1 days), protonymph (3.9?±?0.1 days), deutonymph (4.1?±?0.1 days) and adult (52.6?±?2.2 days) stages. Population parameters and consumption rates suggest that G. aculeifer has good potential as a biological control agent of L. auripila in mushroom production.  相似文献   

8.
The bioassay-guided fractionation of H. oblongifolium has led to the isolation of potent urease inhibitors 1–3. The structures were elucidated by NMR and mass spectroscopic techniques. Compound 2 showed a potent enzyme inhibition activity (IC50 20.96?±?0.93), which is comparatively higher than that for the standard thiourea (IC50 21.01?±?0.51 μM). Compounds 1 and 3 also showed a significant activity, with IC50 37.95?±?1.93 and 138.43?±?1.23 μM, respectively. The sub crude fractions (F1, F2, F3, and F4) were tested in vitro for their urease inhibition activity. Fractions F2 and F4 showed significant activity with IC50 140.37?±?1.93 and 167.43?±?3.03 μM, respectively.  相似文献   

9.
Bismuth compounds are widely used for the treatment of peptic ulcers and Helicobacter pylori infections. It has been suggested that enzyme inhibition plays an important role in the antibacterial activity of bismuth towards this bacterium. Urease, an enzyme that converts urea into ammonia and carbonic acid, is crucial for colonization of the acidic environment of the stomach by H. pylori. Here, we show that three bismuth complexes exhibit distinct mechanisms of urease inhibition, with some differences dependent on the source of the enzyme. Bi(EDTA) and Bi(Cys)3 are competitive inhibitors of jack bean urease with K i values of 1.74 ± 0.14 and 1.84 ± 0.15 mM, while the anti-ulcer drug, ranitidine bismuth citrate (RBC) is a non-competitive inhibitor with a K i value of 1.17 ± 0.09 mM. A 13C NMR study showed that Bi(Cys)3 reacts with jack bean urease during a 30 min incubation, releasing free cysteines from the metal complex. Upon incubation with Bi(EDTA) and RBC, the number of accessible cysteine residues in the homohexameric plant enzyme decreased by 5.80 ± 0.17 and 11.94 ± 0.13, respectively, after 3 h of reaction with dithiobis(2-nitrobenzoic acid). Kinetic analysis showed that Bi(EDTA) is both a competitive inhibitor and a time-dependent inactivator of the recombinant Klebsiella aerogenes urease. The active C319A mutant of the bacterial enzyme displays a significantly reduced sensitivity toward inactivation by Bi(EDTA) compared with the wild-type enzyme, consistent with binding of Bi3+ to the active site cysteine (Cys319) as the mechanism of enzyme inactivation.  相似文献   

10.
Phytochemical investigations were performed on the EtOAc-soluble fraction of the whole plant of the sky flower (Duranta repens) which led to the isolation of the iridoid glycosides 16. Their structures were elucidated by both 1D and 2D NMR spectroscopic analysis. All the compounds showed potent antioxidative scavenging activity in four different tests, with half maximal inhibitory concentration (IC50) values in the range 0.481–0.719?mM against DPPH radicals, 4.07–17.21 µM for the hydroxyl radical (?OH) inhibitory activity test, 43.3–97.37 µM in the total reactive oxygen species (ROS) inhibitory activity test, and 3.39–18.94 µM in the peroxynitrite (ONOO?) scavenging activity test. Duranterectoside A (1) displayed the strongest scavenging potential with IC50 values of (0.481?±?0.06?mM, 4.07?±?0.03, 43.30?±?0.05, 3.39?±?0.02?µM) for the DPPH radicals, ?OH inhibitory activity test, total ROS inhibitory activity test and the ONOO? scavenging activity test, respectively.  相似文献   

11.
Elevated blood glucose and increased activities of secreted phospholipase A2 (sPLA2) are strongly linked to coronary heart disease. In this report, our goal was to develop small heterocyclic compound that inhibit sPLA2. The title compounds were also tested against α-glucosidase and α-amylase. This array of enzymes was selected due to their implication in blood glucose regulation and diabetic cardiovascular complications. Therefore, two distinct series of quinoxalinone derivatives were synthesised; 3-[N′-(substituted-benzylidene)-hydrazino]-1H-quinoxalin-2-ones 3a–f and 1-(substituted-phenyl)-5H-[1,2,4]triazolo[4,3-a]quinoxalin-4-ones 4a–f. Four compounds showed promising enzyme inhibitory effect, compounds 3f and 4b–d potently inhibited the catalytic activities of all of the studied proinflammatory sPLA2. Compound 3e inhibited α-glucosidase (IC50?=?9.99?±?0.18 µM); which is comparable to quercetin (IC50?=?9.93?±?0.66 µM), a known inhibitor of this enzyme. Unfortunately, all compounds showed weak activity against α-amylase (IC50?>?200 µM). Structure-based molecular modelling tools were utilised to rationalise the SAR compared to co-crystal structures with sPLA2-GX as well as α-glucosidase. This report introduces novel compounds with dual activities on biochemically unrelated enzymes mutually involved in diabetes and its complications.  相似文献   

12.
Synechococcus R-2 (PCC 1942) actively accumulates sulphate in the light and dark. Intracellular sulphate was 1.35 ± 0.23 mol m?3 (light) and 0.894 ± 0.152 mol m?3 (dark) under control conditions (BG-11 media: pHo, 7.5; [SO42?]o, 0.304 mol m?3). The sulphate transporter is different from that found in higher plants: it appears to be an ATP-driven pump transporting one SO42?/ATP [ΔμSO42?i,o=+ 27.7 ± 0.24 kJ mol?1 (light) and + 24 ± 0.34 kj mol?1 (dark)]. The rate of metabolism of SO42?at pHo, 7.5 was 150 ± 28 pmol m?2 s?1 (n = 185) in the light but only 12.8 ± 3.6 pmol m?2 s?1 (n = 61) in the dark. Light-driven sulphate uptake is partially inhibited by DCMU and chloramphenicol. Sulphate uptake is not linked to potassium, proton, sodium or chloride transport. The alga has a constitutive over-capacity for sulphate uptake [light (n= 105): Km= 0.3 ± 0.1 mmol m?3, Vmax, = 1.8 ± 0.6 nmol m?2 s?1; dark (n= 56): Km= 1.4 ± 0.4 mmol m?3, Vmax= 41 ± 22 pmol m?2 s?1]. Sulphite (SO32?) was a competitive inhibitor of sulphate uptake. Selenate (SeO42?) was an uncompetitive inhibitor.  相似文献   

13.
Fourteen metronidazole derivatives (compounds 3af and 4bh) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by 1H NMR, MS, and elemental analysis. The inhibitory activities against Helicobacter pylori urease have been investigated in vitro and many compounds have showed promising potential inhibitory activities of H. pylori urease. The effect of compounds 4b (IC50 = 26 μM) and 4g (IC50 = 12 μM) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC50 showed that inhibitor was potent urease inhibitor. A docking analysis using the autodock 4.0 program could explain the inhibitory activities of compound 4g against H. pylori urease.  相似文献   

14.
The square planar Pt(II) complexes of the type [Pt(Ln)(Cl2)] (where Ln = L1?3 = thiophene-2-carboxamide derivatives and L4?6 = thiophene-2-carbothioamide derivatives) have been synthesized and characterized by physicochemical and various spectroscopic studies. MIC method was employed to inference the antibacterial potency of complexes in reference to free ligands and metal salt. Characteristic binding constant (Kb) and binding mode of complexes with calf thymus DNA (CT-DNA) were determined using absorption titration (0.76–1.61 × 105 M?1), hydrodynamic chain length assay and fluorescence quenching analysis, deducing the partial intercalative mode of binding. Molecular docking calculation displayed free energy of binding in the range of –260.06 to –219.63 kJmol?1. The nuclease profile of complexes towards pUC19 DNA shows that the complexes cleave DNA more efficiently compared to their respective metal salt. Cytotoxicity profile of the complexes on the brine shrimp shows that all the complex exhibit noteworthy cytotoxic activity with LC50 values ranging from 7.87 to 15.94 μg/mL. The complexes have been evaluated for cell proliferation potential in human colon carcinoma cells (HCT 116) and IC50 value of complexes by MTT assay (IC50 = 125–1000 μg/mL).  相似文献   

15.
Cholinesterases (ChEs) are enzymes that break down neurotransmitters associated with cognitive function and memory. We isolated cinnamic acids (1 and 2), indolinones (3 and 4), and cycloartane triterpenoid derivatives (519) from the roots of Cimicifuga dahurica (Turcz.) Maxim. by chromatography. These compounds were evaluated for their inhibitory activity toward ChEs. Compound 1 was determined to have an IC50 value of 16.7?±?1.9?μM, and to act as a competitive inhibitor of acetylcholinesterase (AChE). Compounds 3, 4 and 14 were found to be noncompetitive with IC50 values of 13.8?±?1.5 and 6.5?±?2.5?μM, and competitive with an IC50 value of 22.6?±?0.4?μM, respectively, against butyrylcholinesterase (BuChE). Our molecular simulation suggested each key amino acid, Tyr337 of AChE and Asn228 of BuChE, which were corresponded with potential inhibitors 1, and 3 and 4, respectively. Compounds 1 and 4 were revealed to be promising compounds for inhibition of AChEs and BuChEs, respectively.  相似文献   

16.
ABSTRACT

The dissipation and detoxification of nicosulfuron (NS) by Pseudomonas aeruginosa B9 isolated from a cornfield soil was investigated. The fastest decline of NS occurred at 40 µg ml?1 in liquid media with 0.25% glucose plus 0.05% yeast extract (DT50 = 4 days) with a notable pH reduction (pH ? 5). Bioassay tests showed considerable phytotoxicity of NS for Cress (Lepidium sativum L.) with 50% shoot growth inhibition (SGI) at 40 µg ml?1. The dissipation of NS (40 µg ml?1) by the B9 isolate reduced the SGI significantly (SGI: up to 45 ± 3%) compared to the non-inoculated media (SGI: up to 58 ± 4%). In soils with the B9 isolate, NS dissipation, especially at 0.3 µg g?1, was faster with a more significant SGI reduction (k = 0.08 ± 0.00 day?1; SGI = 2 ± 1%) compared to non-inoculated samples (k = 0.03 ± 0.00 day?1; SGI = 8 ± 1%). NS initially inhibited soil respiration, microbial biomass carbon, and dehydrogenase activity. The effect was however transient, and these parameters recovered within 10 days, especially in the presence of the isolate. Overall, this study proves Pseudomonas aeruginosa B9 as a suitable candidate for bioremediation of NS in contaminated sites.  相似文献   

17.
The interaction between K2Cr2O7 and urease was investigated using fluorescence, UV-vis absorption, and circular dichroism (CD) spectroscopy. The experimental results showed that the fluorescence quenching of urease by K2Cr2O7 was a result of the formation of K2Cr2O7–urease complex. The apparent binding constant K A between K2Cr2O7 and urease at 295, 302, and 309 K were obtained to be 2.14?×?104, 1.96?×?104, and 1.92?×?104 L mol?1, respectively. The thermodynamic parameters, Δ and Δ were estimated to be ?5.90 kJ mol?1, 43.67 J mol?1 K?1 according to the Van’t Hoff equation. The electrostatic interaction played a major role in stabilizing the complex. The distance r between donor (urease) and acceptor (K2Cr2O7) was 5.08 nm. The effect of K2Cr2O7 on the conformation of urease was analyzed using UV-vis absorption, CD, synchronous fluorescence spectroscopy, and three-dimensional fluorescence spectra, the environment around Trp and Tyr residues were altered.  相似文献   

18.
Phytochemical investigations on the n-BuOH-soluble fraction of the whole plant of Buddleja davidii led to the isolation of the phenylpropanoid glycosides 1-10. Their structures were determined by 1D and 2D NMR spectroscopic techniques. All the compounds showed potent antioxidative activity in three different tests, with IC50 values in the range 4.15-9.47 μM in the hydroxyl radical (˙OH) inhibitory activity test, 40.32-81.15 μM in the total ROS (reactive oxygen species) inhibitory activity test, and 2.26-7.79 μM in the peroxynitrite (ONOO?) scavenging activity test. Calceolarioside A (1) displayed the strongest scavenging potential with IC50 values of (4.15?±?0.07, 40.32?± 0.09, 2.26?±?0.03μM) for ˙OH, total ROS and scavenging of ONOO?, respectively.  相似文献   

19.
Croplands mainly act as net sources of the greenhouse gases carbon dioxide (CO2) and nitrous oxide (N2O), as well as nitrogen oxide (NO), a precursor of troposheric ozone. We determined the carbon (C) and nitrogen (N) balance of a four-year crop rotation, including maize, wheat, barley and mustard, to provide a base for exploring mitigation options of net emissions. The crop rotation had a positive net ecosystem production (NEP) of 4.4?±?0.7 Mg C ha-1 y-1 but represented a net source of carbon with a net biome production (NBP) of -1.3?±?1.1 Mg C?ha-1 y-1. The nitrogen balance of the rotation was correlated with the carbon balance and resulted in net loss (?24?±?28 kg N ha-1 y-1). The main nitrogen losses were nitrate leaching (?11.7?±1.0 kg N ha-1 y-1) and ammonia volatilization (?9 kg N ha-1 y-1). Dry and wet depositions were 6.7?±?3.0 and 5.9?±0.1 kg N ha-1 y-1, respectively. Fluxes of nitrous (N2O) and nitric (NO) oxides did not contribute significantly to the N budget (N2O: -1.8?±?0.04; NO: -0.7?±?0.04 kg N ha-1 y-1) but N2O fluxes equaled 16% of the total greenhouse gas balance. The link between the carbon and nitrogen balances are discussed. Longer term experiments would be necessary to capture the trends in the carbon and nitrogen budgets within the variability of agricultural ecosystems.  相似文献   

20.
Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer’s disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure–activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50?=?10.2?±?1.2, 16.5?±?1.7, and 15.3?±?1.8?nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.  相似文献   

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