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1.
Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors,Kinetic Mechanism and Molecular Docking
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Aamer Saeed Parvez Ali Mahesar Pervaiz Ali Channar Fayaz Ali Larik Qamar Abbas Mubashir Hassan Hussain Raza Sung‐Yum Seo 《化学与生物多样性》2017,14(8)
The current research article reports the synthesis of coumarinyl pyrazolinyl thioamide derivatives and their biological activity as inhibitors of jack bean urease. The coumarinyl pyrazolinyl thioamides were synthesized by reacting thiosemicarbazide with newly synthesized chalcones to afford the products in good yields and the synthesized compounds were purified by recrystallization. Coumarinyl pyrazolinyl thioamide derivatives 5a – 5q showed significant activity against Urease enzyme and also exhibited good antioxidant potential. The compound 3‐(2‐oxo‐2H‐chromen‐3‐yl)‐5‐phenyl‐4,5‐dihydro‐1H‐pyrazole‐1‐carbothioamide ( 5n ) was found to be superior agent in the series with an IC50 = 0.358 ± 0.017 μm compared to standard thiourea with an IC50 = 4720 ± 174 μm . To undermine the binding mode of inhibition kinetic studies were performed for most potent derivative and it was found that compound 5n inhibits urease enzyme by non‐competitive mode of inhibition. Molecular docking studies were carried out to delineate the binding affinity of the synthesized derivatives. 相似文献
2.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):646-652
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
3.
《Bioorganic & medicinal chemistry》2016,24(18):4452-4463
A facile and robust microwave-assisted solution phase parallel synthesis protocol was exercised for the development of a 38-member library of N,N′-disubstituted thiourea analogues (1–38) by using an identical set of conditions. The reaction time for synthesis of N,N′-disubstituted thiourea analogues was drastically reduced from a reported duration of 8–12 h for conventional methods to only 1.5–2.0 min. All the derivatives (1–38) were characterized by physico-analytical techniques such as elemental analysis in combination with FT-IR, 1H, 13C NMR and by single crystal XRD analysis have also been performed. These compounds were screened for their in vitro urease inhibition activities. Majority of compounds exhibited potent urease inhibition activities, however, the most significant activity was found for 16, with an IC50 value of 1.23 ± 0.1 μM. Furthermore, the synthesized compounds were screened for their cytotoxic potential against lungs cancer cell lines. Cell culture studies demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity were altered in the presence of various side groups. The molecular docking studies of the most potent inhibitors were performed to identify the probable binding modes in the active site of the urease enzymes. These compounds have a great potential and significance for further investigations. 相似文献
4.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):296-299
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
5.
Purification of glutathione S‐transferase enzyme from quail liver tissue and inhibition effects of (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(aryl)acryloyl)phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione derivatives on the enzyme activity
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Yusuf Temel Umit M. Koçyigit M. Şerif Taysı Faik Gökalp Meliha Burcu Gürdere Yakup Budak Mustafa Ceylan İlhami Gülçin Mehmet Çiftci 《Journal of biochemical and molecular toxicology》2018,32(3)
The use of quail meat and eggs has made this animal important in recent years, with its low cost and high yields. Glutathione S‐transferases (GST, E.C.2.5.1.18) are an important enzyme family, which play a critical role in detoxification system. In our study, GST was purified from quail liver tissue with 47.88‐fold purification and 12.33% recovery by glutathione agarose affinity chromatography. The purity of enzyme was checked by SDS‐PAGE method and showed a single band. In addition, inhibition effects of (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(aryl)acryloyl)phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7methanoisoindole‐1,3(2H)‐dion derivatives ( 1a–g ) were investigated on the enzyme activity. The inhibition parameters (IC50 and Ki values) were calculated for these compounds. IC50 values of these derivatives ( 1a–e ) were found as 23.00, 15.75, 115.50, 10.00, and 28.75 μM, respectively. Ki values of these derivatives ( 1a–e ) were calculated in the range of 3.04 ± 0.50 to 131.50 ± 32.50 μM. However, for f and g compounds, the inhibition effects on the enzyme were not found. 相似文献
6.
Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic intervention. Herein, we have synthesized a series of 19 benzofurane linked N-phenyl semithiocarbazones (3a–3s). All the compounds were screened for enzyme inhibitor activity against Jack bean urease. The synthesized N-phenyl thiosemicarbazones had varying activity levels with IC50 values between 0.077 ± 0.001 and 24.04 ± 0.14 μM compared to standard inhibitor, thiourea (IC50 = 21 ± 0.11 μM). The activities of these compounds may be due to their close resemblance of thiourea. A docking study with Jack bean urease (PDB ID: 4H9M) revealed possible binding modes of N-phenyl thiosemicarbazones. 相似文献
7.
《Bioorganic & medicinal chemistry》2014,22(15):4119-4123
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 ± 0.61μM, 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 1H NMR. 相似文献
8.
Synthesis and discovery of potent carbonic anhydrase,acetylcholinesterase, butyrylcholinesterase,and α‐glycosidase enzymes inhibitors: The novel N,N′‐bis‐cyanomethylamine and alkoxymethylamine derivatives
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Parham Taslimi Cuneyt Caglayan Vagif Farzaliyev Oruj Nabiyev Afsun Sujayev Fikret Turkan Ruya Kaya İlhami Gulçin 《Journal of biochemical and molecular toxicology》2018,32(4)
During this investigation, N,N′‐bis‐azidomethylamines, N,N′‐bis‐cyanomethylamine, new alkoxymethylamine and chiral derivatives, which are considered to be a new generation of multifunctional compounds, were synthesized, functional properties were investigated, and anticholinergic and antidiabetic properties of those compounds were studied through the laboratory tests, and it was approved that they contain physiologically active compounds rather than analogues. Novel N‐bis‐cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of the α‐glycosidase, cytosolic carbonic anhydrase I and II isoforms, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with Ki values in the range of 0.15–13.31 nM for α‐glycosidase, 2.77–15.30 nM for human carbonic anhydrase isoenzymes I (hCA I), 3.12–21.90 nM for human carbonic anhydrase isoenzymes II (hCA II), 23.33–73.23 nM for AChE, and 3.84–48.41 nM for BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances. 相似文献
9.
Michal Nowak Wiesaw Tryniszewski Agata Sarniak Anna Wodarczyk Piotr J. Nowak Dariusz Nowak 《Luminescence》2019,34(2):183-192
Oxidative reactions can result in the formation of electronically excited species that undergo radiative decay depending on electronic transition from the excited state to the ground state with subsequent ultra‐weak photon emission (UPE). We investigated the UPE from the Fe2+–EDTA (ethylenediaminetetraacetic acid)–AA (ascorbic acid)–H2O2 (hydrogen peroxide) system with a multitube luminometer (Peltier‐cooled photon counter, spectral range 380–630 nm). The UPE, of 92.6 μmol/L Fe2+, 185.2 μmol/L EDTA, 472 μmol/L AA, 2.6 mmol/L H2O2, reached 1217 ± 118 relative light units during 2 min measurement and was about two times higher (P < 0.001) than the UPE of incomplete systems (Fe2+–AA–H2O2, Fe2+–EDTA–H2O2, AA–H2O2) and medium alone. Substitution of Fe2+ with Cr2+, Co2+, Mn2+ or Cu2+ as well as of EDTA with EGTA (ethylene glycol‐bis(β‐aminoethyl ether)‐N,N,N′,N′‐tetraacetic acid) or citrate powerfully inhibited UPE. Experiments with scavengers of reactive oxygen species (dimethyl sulfoxide, mannitol, sodium azide, superoxide dismutase) revealed the dependence of UPE only on hydroxyl radicals. Dimethyl sulfoxide at the concentration of 0.74 mmol/L inhibited UPE by 79 ± 4%. Plant phenolics (ferulic, chlorogenic and caffec acids) at the concentration of 870 μmol/L strongly enhanced UPE by 5‐, 13.9‐ and 46.8‐times (P < 0.001), respectively. It is suggested that augmentation of UPE from Fe2+–EDTA–AA–H2O2 system can be applied for detection of these phytochemicals. 相似文献
10.
Benzothiazole analogs (1–20) have been synthesized, characterized by EI-MS and 1H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4 ± 0.10 to 34.43 ± 2.10 μM when compared with standard thiourea (IC50 19.46 ± 1.20 μM). Among the series seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N-phenylthiourea 20 with all substituted phenyl derivatives (1–18) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking. 相似文献
11.
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 (IC50 = 11.4 ± 0.4–24.2 ± 1.5 μM) as compared to the standard thiourea (IC50 = 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 CH3, and OCH3 substituents at aryl part were the most potent derivatives. Compound 14 (IC50 = 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 (IC50 = 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. 相似文献
12.
4-Thiazolidinone analogs 1–20 were synthesized, characterized by 1H NMR and EI–MS and investigated for urease inhibitory activity. All twenty (20) analogs exhibited varied degree of urease inhibitory potential with IC50 values 1.73–69.65 μM, if compared with standard thiourea having IC50 value of 21.25 ± 0.15 μM. Among the series, eight derivatives 3, 6, 8, 10, 15, 17, 19, and 20 showed outstanding urease inhibitory potential with IC50 values of 9.34 ± 0.02, 14.62 ± 0.03, 8.43 ± 0.01, 7.3 ± 0.04, 2.31 ± 0.002, 5.75 ± 0.003, 8.81 ± 0.005, and 1.73 ± 0.001 μM, respectively, which is better than the standard thiourea. The remaining analogs showed good to excellent urease inhibition. The binding interactions of these compounds were confirmed through molecular docking studies. 相似文献
13.
Enzyme kinetic studies of inhibition of plant (jackbean) and microbial (Bacillus pasteurii) ureases by eight phosphoroamides [phenylphosphorodiamidate, 4-chlorophenylphosphorodiamidate, phosphoric triamide, N-(diaminophosphinyl)benzamide, N-(diaminophosphinyl)benzeneacetamide, 4-chloro-N-(diaminophosphinyl)benzamide, N-(4-nitrophenyl)phosphoric triamide, N-(diaminophosphinyl)-3-pyridinecarboxamide] demonstrated that these compounds are slow, tight-binding inhibitors of urease enzymes. Measurement of the dissociation constants (Ki*) of the enzyme-inhibitor complexes (E · I*) formed by interaction of the ureases and phosphoroamide inhibitors studied showed that these inhibitors had a much higher affinity (i.e., a lower Ki*) for plant urease than for microbial urease. Measurement of rate constants for formation (kon) and decay (koff) of E · I* showed that, whereas kon varied greatly with the different inhibitors and ureases, koff was constant for the phosphoroamides tested and had a characteristic value for each urease. The half-life of E · I* (30°C; pH 7 THAM buffer) for the plant urease was much longer than that for the microbial urease, and this difference largely accounted for the much higher values of Ki* (koff/kon) observed with microbial urease. 相似文献
14.
Carbonic Anhydrase and Urease Inhibitory Potential of Various Plant Phenolics Using in vitro and in silico Methods
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Abdur Rauf Muslim Raza Muhammad Saleem Ufuk Ozgen Esen Sezen Karaoglan Gulin Renda Erhan Palaska Ilkay Erdogan Orhan 《化学与生物多样性》2017,14(6)
Plant phenolics are known to display many pharmacological activities. In the current study, eight phenolic compounds, e.g., luteolin 5‐O‐β‐glucoside ( 1 ), methyl rosmarinate ( 2 ), apigenin ( 3 ), vicenin 2 ( 4 ), lithospermic acid ( 5 ), soyasaponin II ( 6 ), rubiadin 3‐O‐β‐primeveroside ( 7 ), and 4‐(β‐d ‐glucopyranosyloxy)benzyl 3,4‐dihydroxybenzoate ( 8 ), isolated from various plant species were tested at 0.2 mm against carbonic anhydrase‐II (CA‐II) and urease using microtiter assays. Urease inhibition rate for compounds 1 – 8 ranged between 5.0 – 41.7%, while only compounds 1 , 2 , and 4 showed a considerable inhibition over 50% against CA‐II with the IC50 values of 73.5 ± 1.05, 39.5 ± 1.14, and 104.5 ± 2.50 μm , respectively, where IC50 of the reference (acetazolamide) was 21.0 ± 0.12 μm . In silico experiments were also performed through two docking softwares (Autodock Vina and i‐GEMDOCK) in order to find out interactions between the compounds and CA‐II. Actually, compounds 6 (30.0%) and 7 (42.0%) possessed a better binding capability toward the active site of CA‐II. According to our results obtained in this study, among the phenolic compounds screened, particularly 1 , 2 , and 4 appear to be the promising inhibitors of CA‐II and may be further investigated as possible leads for diuretic, anti‐glaucoma, and antiepileptic agents. 相似文献
15.
Jin-Ha Jeong Young-Dong Jeon O-Mi Lee Jeong-Do Kim Na-Ri Lee Geun-Tae Park Hong-Joo Son 《Biodegradation》2010,21(6):1029-1040
In this study, we isolated and characterized a novel feather-degrading bacterium that shows keratinolytic, antifungal and
plant growth-promoting activities. A bacterium S8 was isolated from forest soil and confirmed to belong to Bacillus subtilis by BIOLOG system and 16S rRNA gene analysis. The improved culture conditions for the production of keratinolytic protease
were 0.1% (w/v) sorbitol, 0.3% (w/v) KNO3, 0.1% (w/v) K2HPO4, 0.06% (w/v) KH2PO4 and 0.04% (w/v) MgCl2·6H2O (pH 8.0 and 30°C), respectively. In the improved medium containing 0.1% (w/v) feather, keratinolytic protease production
was around 53.3 ± 0.3 U/ml at 4 day; this value was 10-fold higher than the yield in the basal feather medium (5.3 ± 0.1 U/ml).
After cultivation for 5 days in the improved medium, intact feather was completely degraded. Feather degradation resulted
in free –SH group, soluble protein and amino acids production. The concentration of free –SH group in the culture medium was
15.5 ± 0.2 μM at 4 days. Nineteen amino acids including all essential amino acids were produced in the culture medium; the
concentration of total amino acid produced was 3360.4 μM. Proline (2809.9 μM), histidine (371.3 μM) and phenylalanine (172.0 μM)
were the major amino acids released in the culture medium. B. subtilis S8 showed the properties related to plant growth promotion: hydrolytic enzymes, ammonification, indoleacetic acid (IAA),
phosphate solubilization, and broad-spectrum antimicrobial activity. Interestingly, the strain S8 grown in the improved medium
produced IAA and antifungal activity, indicating simultaneous production of keratinolytic and antifungal activities and IAA
by B. subtilis S8. These results suggest that B. subtilis S8 could be not only used to improve the nutritional value of feather wastes but also is useful in situ biodegradation of
feather wastes. Furthermore, it could also be a potential biofertilizer or biocontrol agent applicable to crop plant soil. 相似文献
16.
High‐performance liquid chromatographic enantioseparation of N‐aryl‐thioureidoalkylphosphonates and thiourylenedi(alkylphosphonates) on polysaccharide‐based chiral stationary phases
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Józef Drabowicz Marcin H. Kudzin Zbigniew H. Kudzin Patrycja Pokora‐Sobczak 《Chirality》2018,30(2):131-140
The first successful enantioseparation of representative O,O‐diphenyl‐N‐arylthioureidoalkylphosphonates, (±)‐Ptc‐ValP(OPh)2 & (±)‐Ptc‐LeuP(OPh)2 and thiourylenedi(isobutyl phosphonate), Tcm[ValP(OPh)2]2 on analytical and semipreparative scale was achieved by high‐performance liquid chromatography using polysaccharide‐based chiral stationary phases (CPs). Atc‐AAP(OPh)2 was obtained using modified tricomponent condensations of the corresponding aldehydes, N‐arylthiourea and triphenyl phosphite whereas Tcm[ValP(OPh)2]2 by the condensations of aldehydes, thiourea, and triphenyl phosphite. The prepared, racemic (±)‐Atc‐AAP(OPh)2 [(±)‐Ptc‐ValP(OPh)2, (±)‐Ptc‐LeuP(OPh)2, (±)‐Ptc‐PglyP(OPh)2 and (±)‐Ntc‐PglyP(OPh)2] and racemic (±)‐Tcm[AAP(OPh)2]2 [(±)‐Tcm[NvaP(OPh)2]2 & (±)‐Tcm[ValP(OPh)2]2] were adequately characterized and used for chromatographic separations on high‐performance liquid chromatography–chiral stationary phases. The best results were obtained for (±)‐Ptc‐ValP(OPh)2, (±)‐Ptc‐LeuP(OPh)2 and (±)‐Tcm[ValP(OPh)2]2. 相似文献
17.
A library of 4,6-dihydroxypyrimidine diones (1–35) were synthesized and evaluated for their urease inhibitory activity. Structure-activity relationships, and mechanism of inhibition were also studied. All compounds were found to be active with IC50 values between 22.6 ± 1.14–117.4 ± 0.73 µM, in comparison to standard, thiourea (IC50 = 21.2 ± 1.3 µM). Kinetics studies on the most active compounds 2–7, 16, 17, 28, and 33 were performed to investigate their modes of inhibition, and dissociation constants Ki. Compounds 2, 3, 7, 16, 28, and 33 were found to be mixed-type of inhibitors with Ki values in the range of 7.91 ± 0.024–13.03 ± 0.013 µM, whereas, compounds 4–6, and 17 were found to be non-competitive inhibitors with Ki values in the range of 9.28 ± 0.019–13.05 ± 0.023 µM. In silico study was also performed, and a good correlation was observed between experimental and docking studies. This study is continuation of our previously reported urease inhibitory activity of pyrimidine diones, representing potential leads for further research as possible treatment of diseases caused by ureolytic bacteria. 相似文献
18.
《Bioorganic & medicinal chemistry》2016,24(19):4519-4527
Helicobacter pylori urease is involved in several physiologic responses such as stomach and duodenal ulcers, adenocarcinomas and stomach lymphomas. Thus, inhibition of urease is taken for a good chance to treat H. pylori-caused infections, we have therefore focused our efforts on seeking novel urease inhibitors. Here, a series of arylpropionylhydroxamic acids were synthesized and evaluated for urease inhibition. Out of these compounds, 3-(2-benzyloxy-5-chlorophenyl)-3-hydroxypropionylhydroxamic acid (d24) was the most active inhibitor with IC50 of 0.15 ± 0.05 μM, showing a mixed inhibition with both competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives kinetics parameters of 0.13 and 0.12 μg·mL−1 for Ki and Ki′, respectively. The plasma protein binding assays suggested that d24 exhibited moderate binding to human and rabbit plasma proteins. 相似文献
19.
Li F Chvyrkova I Terzyan S Wakeham N Turner R Ghosh AK Zhang XC Tang J 《Applied microbiology and biotechnology》2012,94(4):1041-1049
The metalloprotease activity of lethal factor (LF) from Bacillus anthracis (B. anthracis) is a main source of toxicity in the lethality of anthrax infection. Thus, the understanding of the enzymatic activity and
inhibition of B. anthracis LF is of scientific and clinical interests. We have designed, synthesized, and studied a peptide inhibitor of LF, R9LF-1,
with the structure NH2–(d-Arg)9–Val–Leu–Arg–CO–NHOH in which the C-terminal hydroxamic acid is commonly used in the inhibitors of metalloproteases to chelate
the active-site zinc. This inhibitor was shown to be very stable in solution and effectively inhibited LF in kinetic assays.
However, its protection on murine macrophages against lethal toxin’s lysis activity was relatively weak in longer assays.
We further observed that the hydroxamic acid group in R9LF-1 was hydrolyzed by LF, and the hydrolytic product of this inhibitor
is considerably weaker in inhibition of potency. To resist this unique hydrolytic activity of LF, we further designed a new
inhibitor R9LF-2 which contained the same structure as R9LF-1 except replacing the hydroxamic acid group with N,O-dimethyl hydroxamic acid (DMHA), –N(CH3)–O–CH3. R9LF-2 was not hydrolyzed by LF in long-term incubation. It has a high inhibitory potency vs. LF with an inhibition constant
of 6.4 nM had a better protection of macrophages against LF toxicity than R9LF-1. These results suggest that in the development
of new LF inhibitors, the stability of the chelating group should be carefully examined and that DMHA is a potentially useful
moiety to be used in new LF inhibitors. 相似文献
20.
Diurnal and seasonal trends in net photosynthetic rate (P
N), stomatal conductance (g), transpiration rate (E), vapour pressure deficit, temperature, photosynthetic photon flux density, and water use efficiency (WUE) were compared
in a two-year-old Dalbergia sissoo and Hardwickia binata plantation. Mean daily maximum P
N in D. sissoo ranged from 21.40±2.60 μmol m−2 s−1 in rainy season I to 13.21±2.64 μmol m−2 s−1 in summer whereas in H. binata it was 20.04±1.20 μmol m−2 s−1 in summer and 13.64±0.16 μmol m−2 s−1 in winter. There was a linear relationship between daily maximum P
N and g
s in D. sissoo but there was no strong linear relationship between P
N and g
s in H. binata. In D. sissoo, the reduction in g
s led to a reduction in both P
N and E enabling the maintenance of WUE during dry season thereby managing unfavourable environmental conditions efficiently whereas
in H. binata, an increase in g
s causes an increase of P
N and E with a significant moderate WUE. 相似文献