共查询到20条相似文献,搜索用时 15 毫秒
1.
Battagim J Souza VT Miyasaka NR Cunha IB Sawaya AC Fernandes AM Eberlin MN Ribeiro ML Carvalho Pde O 《Journal of enzyme inhibition and medicinal chemistry》2012,27(2):232-240
Glucosyltransferase (GTF) plays an important role in the development of dental caries. This study was carried out to compare the efficiency of green mate (GM) and roasted mate (RM) water extracts, drinks rich in polyphenolic compounds consumed in the subtropical region of South America, on the extracellular GTF activity from Streptococcus mutans. The RM extract exhibited a greater inhibitory effect (IC?? of 10 mg/mL) despite presenting lower polyphenolic content. The kinetic analysis showed that there were significant differences (P?0.05) between the extracts with respect to the values for K(m) and K(i), whereas the values for V(max) were the same, implying the competitive nature of GTF inhibition. GTF activity was also measured using selected polyphenols as inhibitors, and the most effective inhibitors were rutin and caffeoylshikimic acid. The characterization of the extracts by ESI-MS and UPLC-MS showed that the compounds formed during roasting, possibly shikimic acid derivatives and other unindentified compounds formed by the Maillard reaction, appeared to contribute to the inhibition of GTF activity. 相似文献
2.
Yukinori Yabuta Haruka Mukoyama Yoshimi Kaneda Narisa Kimura Tomohiro Bito Tsuyoshi Ichiyanagi 《Bioscience, biotechnology, and biochemistry》2018,82(9):1584-1590
Streptococcus mutans is a bacterium found in human oral biofilms (dental plaques) that is associated with the development of dental caries. Glucosyltransferases (GTFs) are key enzymes involved in dental plaque formation, and compounds that inhibit their activities may prevent dental caries. We developed a screening system for GTF-inhibitory activities, and used it to profile 44 types of herbal tea extracts. Lemon myrtle (Backhousia citriodora) extract exhibited the highest GTF-inhibitory activity, with an IC50 for GTF in solution of 0.14 mg mL?1. Furthermore, lemon myrtle extracts had the third-highest polyphenol content of all tested extracts, and strongly inhibited S. mutans biofilm. Interestingly, lemon myrtle extracts did not inhibit cell growth. 相似文献
3.
Özlen Güzel-Akdemir Andrea Angeli Kübra Demir Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1299-1308
A small collection of 26 structurally novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group, were synthesised and tested in enzyme inhibition assays against the tumour-associated hCA IX enzyme. Inhibition constants in the lower micromolar region (KI 25?μM) have been measured for 17 of the 26 compounds. Even though the KI values are relatively weak, the fact that they do not contain a sulphonamide moiety suggests that these compounds do not interact with the active site zinc ion. Therefore, docking studies and molecular dynamics simulations have been performed to suggest binding poses for these structurally novel inhibitors. 相似文献
4.
《Bioscience, biotechnology, and biochemistry》2013,77(12):2351-2358
A series of polyphenolic curcumin analogs were synthesized and their inhibitory effects on mushroom tyrosinase and the inhibition of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical formation were evaluated. The results indictated that the analogs possessing m-diphenols and o-diphenols exhibited more potent inhibitory activity on tyrosinase than reference compound rojic acid, and that the analogs with o-diphenols exhibited more potent inhibitory activity of DPPH free-radical formation than reference compound vitamin C. The inhibition kinetics, analyzed by Lineweaver–Burk plots, revealed that compounds B2 and C2 bearing o-diphenols were non-competitive inhibitors, while compounds B11 and C11 bearing m-diphenols were competitive inhibitors. In particular, representative compounds C2 and B11 showed no side effects at a dose of 2,000 mg/kg in a preliminary evaluation of acute toxicity in mice. These results suggest that such polyphenolic curcumin analogs might serve as lead compounds for further design of new potential tyrosinase inhibitors. 相似文献
5.
Wen-Hua Zhao ChunChun Gao Ying-Xia Zhang Wei-Xi Tian 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):501-510
Fatty acid synthase (FAS) is a very significant lipogenic enzyme participating in energy metabolism in vivo and has been reported as a potential new therapeutic target for cancer treatment. The extracts from sixteen Aceraceae were prepared to assay their inhibitory activities against duck liver FAS and their correlated antitumor bioactivity. Their inhibition of FAS was composed of a reversible fast-binding inhibition, by which 0.41 μg/mL of the A. campestre extract inhibits 50% FAS activity, and an irreversible slow-binding inhibition with inactivation rate constants, kobs, ranging between 1.5 × 10? 3 and 10.6 × 10? 3 min? 1. Three Aceraceae extracts were selected from their smaller IC50 values to study different type of inhibitions against the three substrates in the FAS overall reaction. As compared with other reported FAS inhibitors including EGCG with regard to inhibition constant and IC50 value, the extracts appeared to be more efficient inhibitors, and exhibited a considerable inhibition against the growth of five types of cancer cells (China patent application number 200610088901.6), which may be related to the inhibition of lipogenesis in these cells. 相似文献
6.
A. Djeridane M. Yousfi B. Nadjemi S. Maamri F. Djireb P. Stocker 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):719-726
Carboxylesterases (CE), expressed at high levels in human liver and intestine, are thought to detoxify xenobiotics. The goal of this study was to study the effect of phenolic compounds from several plants from the Algerian Atlas used traditionally in Arab folk medicine on the enzymatic activity of porcine liver carboxylesterase. The plants have shown a potent inhibition of carboxylesterase (CE) enzymatic activity in a concentration-dependent manner. Results indicate that the Phenolic extracts from these plants lead to the inactivation of the CE pI = 5.1 with Ki values in micromolar range (1.4–38 μM). These results encourage further biological investigation and identification the inhibitors responsible for this activity. 相似文献
7.
Pyruvate kinase isoenzyme M2 (PKM2) is one of the most important control point enzyme in glycolysis pathway. Hence, its inhibitors and activators are currently considered as the potential anticancer agents. The effect of 28 polyphenolic compounds on the enzyme activity was investigated in vitro. Among these compounds, neoeriocitrin, (?)-catechin gallate, fisetin, (±)-taxifolin and (?)-epicatechin have the highest inhibition effect with IC50 value within 0.65–1.33?µM range. Myricetin and quercetin 3-β-d-glucoside exhibited the highest activation effect with 0.51 and 1.34?µM AC50 values, respectively. Twelve of the compounds showed inhibition effect within 7–38?µM range of IC50 value. Sinapinic acid and p-coumaric acid showed an activation effect with 26.2 and 22.2?µM AC50 values, respectively. The results propose that the polyphenolics may be the potential PKM2 inhibitors/activators, and they may be used as lead compounds for the synthesis of new inhibitors or activators of this enzyme. 相似文献
8.
N. M. Useh A. J. Nok S. F. Ambali K. A. N. Esievo 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):339-342
The inhibition of neuraminidase from Clostridium chauvoei (jakari strain) with partially purified methanolic extracts of some plants used in Ethnopharmacological practice was evaluated. Extracts of two medicinal plants, Tamarindus indicus and Combretum fragrans at 100–1000 μg/ml, both significantly reduced the activity of the enzyme in a dose-dependent fashion (P < 0.001).The estimated IC50 values for Tamarindus indicus and Combretum fragrans were 100 and 150 μ/ml respectively. Initial velocity studies conducted, using fetuin as substrate revealed a non-competitive inhibition with the Vmax significantly altered from 500 μmole min?1 mg?1 to 240μmole min?1 mg?1 and 340 μmole min?1 mg?1 in the presence of Tamarindus indicus and Combretum fragrans respectively. The KM remained unchanged at 0.42 mM. The computed Index of physiological efficiency was reduced from 1.19 min?1 to 0.57 min?1 and 0.75 min?1 with Tamarindus indicus and Combretum fragrans as inhibitors respectively. 相似文献
9.
Rosanna Caliandro Alessandro Pesaresi Luca Cariati Antonio Procopio Manuela Oliverio 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):794-803
Acetylcholinesterase inhibitors were introduced for the symptomatic treatment of Alzheimer’s disease (AD). Among the currently approved inhibitors, donepezil (DNP) is one of the most preferred choices in AD therapy. The X-ray crystal structures of Torpedo californica AChE in complex with two novel rigid DNP-like analogs, compounds 1 and 2, have been determined. Kinetic studies indicated that compounds 1 and 2 show a mixed-type inhibition against TcAChE, with Ki values of 11.12?±?2.88 and 29.86?±?1.12?nM, respectively. The DNP rigidification results in a likely entropy-enthalpy compensation with solvation effects contributing primarily to AChE binding affinity. Molecular docking evidenced the molecular basis for the binding of compounds 1 and 2 to the active site of β-secretase-1. Overall, these simplified DNP derivatives may represent new structural templates for the design of lead compounds for a more effective therapeutic strategy against AD by foreseeing a dual AChE and BACE-1 inhibitory activity. 相似文献
10.
Victor Muleya Rose Hayeshi Hilary Ranson Berhanu Abegaz Merha-Tibeb Bezabih Metuno Robert 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):391-399
Elevated glutathione transferase (GST) E2 activity is associated with DDT resistance in the mosquito Anopheles gambiae. The search for chemomodulators that inhibit the function of AgGSTE2 would enhance the insecticidal activity of DDT. Therefore, we examined the interaction of novel natural plant products with heterologously expressed An. gambiae GSTE 2 in vitro. Five of the ten compounds, epiphyllocoumarin (Tral-1), knipholone anthrone, isofuranonaphthoquinones (Mr 13/2, Mr13/4) and the polyprenylated benzophenone (GG1) were shown to be potent inhibitors of AgGSTE2 with IC50 values of 1.5 μM, 3.5 μM, 4 μM, 4.3 μM and 4.8 μM respectively. Non-competitive inhibition was obtained for Tral 1 and GG1 with regards to GSH (Ki of 0.24 μM and 0.14 μM respectively). Competitive inhibition for Tral1 was obtained with CDNB (Ki = 0.4 μM) whilst GG1 produced mixed type of inhibition. The Ki and Ki' for GSH for Tral-1 and GG1 were 0.2 μM and 0.1 μM respectively. These results suggest that the novel natural plant products, particularly Tral-1, represent potent AgGSTE2 in vitro inhibitors. 相似文献
11.
Marcin Skoreński Aleksandra Milewska Krzysztof Pyrć Marcin Sieńczyk 《Journal of enzyme inhibition and medicinal chemistry》2019,34(1):8-14
West Nile virus (WNV) is a member of the flavivirus genus belonging to the Flaviviridae family. The viral serine protease NS2B/NS3 has been considered an attractive target for the development of anti-WNV agents. Although several NS2B/NS3 protease inhibitors have been described so far, most of them are reversible inhibitors. Herein, we present a series of α-aminoalkylphosphonate diphenyl esters and their peptidyl derivatives as potent inhibitors of the NS2B/NS3 protease. The most potent inhibitor identified was Cbz-Lys-Arg-(4-GuPhe)P(OPh)2 displaying Ki and k2/Ki values of 0.4 µM and 28 265 M?1s?1, respectively, with no significant inhibition of trypsin, cathepsin G, and HAT protease. 相似文献
12.
Chemical Composition of Roots Flemingia philippinensis and Their Inhibitory Kinetics on Aromatase
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Aromatase is the key enzyme responsible for catalyzing the conversion of C19 steroids to estrogens. Its inhibitors are widely used in breast cancer therapy. The CH2Cl2 partition of a crude ethanolic extract from the roots of Flemingia philippinensis showed potent inhibitory activity of aromatase. The constituents of the extract were analyzed and identified by liquid chromatography tandem mass spectrometry. Five purified prenylated isoflavones were evaluated for aromatase inhibition and their IC50 values ranged between 2.98 and 58.08 μm . In kinetic studies, all tested compounds behaved as reversible competitive inhibitors and their Ki values were calculated by Dixon plots. The most potent inhibitor (6,8‐diprenylorobol) had a Ki value of 1.42 μm . Furthermore, using UPLC and LC/MS, 6,8‐diprenylorobol was proven to be present in the native roots in high quantities. 相似文献
13.
M. Alijanianzadeh A. A. Saboury H. MANSURI-TORSHIZI K. HAGHBEEN A. A. MOOSAVI-MOVAHEDI 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):239-246
Three iso-alkyldithiocarbonates (xanthates), as sodium salts, C3H7OCS2Na (I), C4H9OCS2Na (II) and C5H11OCS2Na (III), were synthesized, by the reaction between CS2 with the corresponding iso-alcohol in the presence of NaOH, and examined for inhibition of both cresolase and catecholase activities of mushroom tyrosinase (MT) from a commercial source of Agricus bisporus. 4-[(4-methylbenzo)azo]-1,2-benzendiol (MeBACat) and 4-[(4-methylphenyl)azo]-phenol (MePAPh) were used as synthetic substrates for the enzyme for the catecholase and cresolase reactions, respectively. Lineweaver-Burk plots showed different patterns of mixed and competitive inhibition for the three xanthates and also for cresolase and catecholase activities of MT. For cresolase activity, I and II showed a mixed inhibition pattern but III showed a competitive inhibition pattern. For catecholase activity, I showed mixed inhibition but II and III showed competitive inhibition. These new synthesized compounds are potent inhibitors of MT with Ki values of 9.8, 7.2 and 6.1 μM for cresolase inhibitory activity, and also 12.9, 21.8 and 42.2 μM for catecholase inhibitory activity for I, II and III, respectively. They showed a greater inhibitory potency towards the cresolase activity of MT. Both substrate and inhibitor can be bound to the enzyme with negative cooperativity between the binding sites (α>1) and this negative cooperativity increases with increasing length of the aliphatic tail in these compounds in both cresolase and catecholase activities. The cresolase inhibition is related to the chelating of the copper ions at the active site by a negative head group (S? ) of the anion xanthate, which leads to similar values of Ki for all three xanthates. Different Ki values for catecholase inhibition are related to different interactions of the aliphatic chains of I, II and III with hydrophobic pockets in the active site of the enzyme. 相似文献
14.
Emanuela Berrino Murat Bozdag Sonia Del Prete Fatmah A. S. Alasmary Linah S. Alqahtani Zeid AlOthman 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1194-1198
The inhibition of α-, β-, γ-, and δ-class carbonic anhydrases (CAs, EC 4.2.1.1) from bacteria (Vibrio cholerae and Porphyromonas gingivalis) and diatoms (Thalassiosira weissflogii) with a panel of N’-aryl-N-hydroxy-ureas is reported. The α-/β-CAs from V. cholerae (VchCAα and VchCAβ) were effectively inhibited by some of these derivatives, with KIs in the range of 97.5?nM – 7.26?µM and 52.5?nM – 1.81?µM, respectively, whereas the γ-class enzyme VchCAγ was less sensitive to inhibition (KIs of 4.75 – 8.87?µM). The β-CA from the pathogenic bacterium Porphyromonas gingivalis (PgiCAβ) was not inhibited by these compounds (KIs?>?10?µM) whereas the corresponding γ-class enzyme (PgiCAγ) was effectively inhibited (KIs of 59.8?nM – 6.42?µM). The δ-CA from the diatom Thalassiosira weissflogii (TweCAδ) showed effective inhibition with these derivatives (KIs of 33.3?nM – 8.74?µM). As most of these N-hydroxyureas are also ineffective as inhibitors of the human (h) widespread isoforms hCA I and II (KIs?>?10?µM), this class of derivatives may lead to the development of CA inhibitors selective for bacterial/diatom enzymes over their human counterparts and thus to anti-infectives or agents with environmental applications. 相似文献
15.
Wei Chen Shengqiang Shen Lili Dong Jianjun Zhang Qing Yang 《Bioorganic & medicinal chemistry》2018,26(2):394-400
To develop selective inhibitors for β-N-acetylhexosaminidases which are involved in a myriad of physiological processes, a series of novel thioglycosyl–naphthalimide hybrid inhibitors were designed, synthesized and evaluated for inhibition activity against glycosyl hydrolase family 20 and 84 (GH20 and GH84) β-N-acetylhexosaminidases. These compounds which incorporate groups with varied sizes and lengths at the linker region between thioglycosyl moiety and naphthalimide moiety are designed to improve the selectivity and stacking interactions. The GH84 human O-GlcNAcase (hOGA) was sensitive to the subtle changes in the linker region and the optimal choice is a small size linker with six atoms length. And the GH20 insect β-N-acetylhexosaminidase OfHex1 could tolerate compounds with a hydrophobic bulky linker. Especially, the compound 5c (hOGA, Ki?=?3.46?μM; OfHex1, Ki?>?200?μM) and the compound 6f (hOGA, Ki?>?200?μM; OfHex1, Ki?=?21.81?μM) displayed high selectivity. The molecular docking results indicated that the inhibition mechanism was different between the two families due to their different structural characteristics beyond the active sites. These results provide some promising clues to improve selectivity of potent molecules against β-N-acetylhexosaminidases. 相似文献
16.
《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
17.
18.
Mahmoud Balbaa Mohamed Abdel-Megeed Thoria Diab Hamdy Mansour 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):483-492
Quinazolinone derivatives have been studied as both in vitro and in vivo inhibitors of aspartate transcarbamylase (ATCase). In vitro treatment of mammalian ATCase with four compounds revealed that they inhibited enzyme activity and that 2-phenyl-1,3-4(H)benzothiazin-4-thione was the most potent one. This compound acts as a noncompetitive inhibitor towards both aspartate and carbamoyl phosphate. The values of the inhibition constant (Ki) indicate that this compound exerts a potent inhibitory effect upon ATCase activity. Moreover, in vivo treatment with different doses of these derivatives showed also an inhibitory effect upon ATCase, the relative activity being decreased by 40%–58% with a 1 mg dose. These data support the inhibition of ATCase by quinazolinone derivatives as a new type of inhibitor for the enzyme. 相似文献
19.
Sarno S Ruzzene M Frascella P Pagano MA Meggio F Zambon A Mazzorana M Di Maira G Lucchini V Pinna LA 《Molecular and cellular biochemistry》2005,274(1-2):69-76
A number of quite specific and fairly potent inhibitors of protein kinase CK2, belonging to the classes of condensed polyphenolic compounds, tetrabromobenzimidazole/triazole derivatives and indoloquinazolines are available to date. The structural basis for their selectivity is provided by a hydrophobic pocket adjacent to the ATP/GTP binding site, which in CK2 is smaller than in the majority of other protein kinases due to the presence of a number of residues whose bulky side chains are generally replaced by smaller ones. Consequently a doubly substituted CK2 mutant V66A,I174A is much less sensitive than CK2 wild type to these classes of inhibitors. The most efficient inhibitors both in terms of potency and selectivity are 4,5,6,7-tetrabromo-1H-benzotriazole, TBB (Ki = 0.4 μM), the TBB derivative 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole, DMAT (Ki = 0.040 μM), the emodin related coumarinic compound 8-hydroxy-4-methyl-9-nitrobenzo[g]chromen-2-one, NBC (Ki = 0.22 μM) and the indoloquinazoline derivative ([5-oxo-5,6-dihydroindolo-(1,2a)quinazolin-7-yl]acetic acid), IQA (Ki = 0.17 μM). These inhibitors are cell permeable as judged from ability to block CK2 in living cells and they have been successfully employed, either alone or in combination with CK2 mutants refractory to inhibition, to dissect signaling pathways affected by CK2 and to identify the endogenous substrates of this pleitropic kinase. By blocking CK2 these inhibitors display a remarkable pro-apoptotic efficacy on a number of tumor derived cell lines, a property which can be exploited in perspective to develop antineoplastic drugs. 相似文献
20.
Of 13 compounds tested, 11 inhibited malic enzyme activity in Mucor circinelloides, to some degree, at 5 mM. Four of these inhibitors (tartronic acid, morin, catechin and 2,5-dihydroxybenzoic acid) were studied
further. Tartronic acid, morin and catechin were competitive inhibitors of malic enzyme (with respect to malate), with apparent
Ki values of 0.04 mM, 5 μM and 0.6 mM, respectively. 2,5-Dihydroxybenzoic acid was a non-competitive inhibitor, with respect
to malate, and had an apparent Ki value of 0.8 mM. Morin and tartronic acid did not inhibit any other NADPH-generating enzyme studied, although both inhibited
malate dehydrogenase. The inhibitory actions of catechin and 2,5-dihydroxybenzoic acid were less specific. All four compounds
inhibited malic enzyme, to some extent, when included in the culture medium. This inhibition was not as great as in vitro however and was insufficient to have an effect on lipid metabolism in M. circinelloides.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献