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Results 251 - 300 of 2158
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Kurosumi Motonori - - 2010
Screening of our library of peroxisome proliferator-activated receptor (PPAR) agonists yielded several phenylpropanoic acid-derived gamma-secretase inhibitors (GSIs). Structure-activity relationship studies indicated that (R)-configuration of alpha-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs.
Ghizzoni Massimo - - 2010
Several lines of evidence indicate that histone acetyltransferases (HATs) are novel drug targets for treatment of diseases like, for example, cancer and inflammation. The natural product anacardic acid is a starting point for development of small molecule inhibitors of the histone acetyltransferase (HAT) p300/CBP associated factor (PCAF). In order to ...
Hnilickova Jaroslava - - 2010
Androstane brassinosteroid analogues with alpha-azido acid ester groups in position 17beta were synthesized from 2alpha,3alpha,17beta-trihydroxy-5alpha-androstan-6-one after the protection of the 2alpha,3alpha-diols upon treatment with the corresponding alpha-azido acid and the subsequent deprotection of the diol grouping. Six new castasterone analogues were prepared. The biological activities were evaluated in two bioassays: ...
Anselm Lilli - - 2010
A series of (3R,4R)-pyrrolidine-3,4-dicarboxylic acid amides was investigated with respect to their factor Xa inhibitory activity, selectivity, pharmacokinetic properties, and ex vivo antithrombotic activity. The clinical candidate from this series, R1663, exhibits excellent selectivity against a panel of serine proteases and good pharmacokinetic properties in rats and monkeys. A Phase ...
Ramsdell John S - - 2010
Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe ...
Ngai Mun H - - 2010
Using click chemistry to enable both structural diversity and proteome profiling within a natural product derived library, two out of nineteen lipstatin analogues showed similar activity to Orlistat against fatty acid synthase (FAS), but with an improved ability to induce tumour cell death.
Gattinoni Sonia - - 2010
A series of oxime carbamates have been identified as potent inhibitors of fatty acid amide hydrolase (FAAH), an important regulatory enzyme of the endocannabinoid signaling system. Kinetic analysis indicates that they behave as non-competitive, reversible inhibitors, and show remarkable selectivity for FAAH over the other components of the endocannabinoid system.
Kyi Stella - - 2010
A series of novel polyacetylene substituted 2-hydroxy acids and derivatives were prepared and characterized. Alkylation of butane-2,3-diacetal (BDA) protected glycolic acid with iodoalkyl substituted polyacetylene compounds gave the corresponding diacetal protected polyacetylene substituted 2-hydroxy acids. Diacetal deprotection through acid mediated hydrolysis, transesterification or aminolysis afforded the 2-hydroxy-polyacetylenic acid, ester or ...
Carrillo Adela I - - 2010
Al-containing helical mesoporous silicas have been synthesized and characterised by different techniques, showing outstanding activities (comparable to those obtained with sulfuric acid) in the oxathioacetalization of cyclohexane.
Gondela Edyta - - 2010
5-(Omega-hydroxyalkylamino) derivatives of mucochloric acids were synthesized through a facile substitution reaction of 3,4-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid) acetate or 5-methylcarbonate with an appropriate amino alcohol or aminodiol. The obtained products were characterized and screened for their antibacterial and antiprotozoal activities.
Dawson Marcia I - - 2010
Increasing evidence demonstrates that three classes of molecules originally derived from all-trans-retinoic acid and its synthetic analogues, which function by interacting with the retinoid nuclear receptors, exert their anticancer activities through alternative signaling pathways. Thus, the methylene-linked analogues (4-HBR, 4-HPRCG, and 4-HBRCG) of N-(4-hydroxyphenyl) retinamide (4-HPR) and its O-glucuronide metabolite ...
Na MinKyun - - 2010
Inhibition of fatty acid synthase (FAS) has been proposed to be a new therapeutic target for the treatment of cancer and obesity. In our preliminary screening study on the FAS inhibitory activity, a n-hexane soluble fraction prepared from the fruit of Schisandra chinensis (Schisandraceae) was found to inhibit FAS activity ...
Ilies Monica - - 2010
Arginase, a key metalloenzyme of the urea cycle that converts L-arginine into L-ornithine and urea, is presently considered a pharmaceutical target for the management of diseases associated with aberrant l-arginine homeostasis, such as asthma, cardiovascular diseases, and erectile dysfunction. We now report the design, synthesis, and evaluation of a series ...
Meinerz Daiane Francine - - 2011
(S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate, a new telluroamino acid derivative, showed remarkable glutathione peroxidase (GPx)-like activity, attesting to its antioxidant potential. However, the stability and toxicity of this compound has not yet been investigated. The present study was designed to investigate the pharmacological/toxicological properties of this compound in vitro and in ...
Khan Sher Bahadar - - 2010
A series of benzoic acid derivatives 1-10 have been synthesised by two different methods. Compounds 1-6 were synthesised by a facile procedure for esterification using N,N'-dicyclohexylcarbodiimide (DCC) as a coupling agent, methylene chloride as a solvent system and dimethylaminopyridine (DMAP). While 7-10 were synthesised by converting benzoic acid into benzoyl ...
McKenna Charles E - - 2010
3-(3-Pyridyl)-2-hydroxy-2-phosphonopropanoic acid (3-PEHPC, 1) is a phosphonocarboxylate (PC) analogue of 2-(3-pyridyl)-1-hydroxyethylidenebis(phosphonic acid) (risedronic acid, 2), an osteoporosis drug that decreases bone resorption by inhibiting farnesyl pyrophosphate synthase (FPPS) in osteoclasts, preventing protein prenylation. 1 has lower bone affinity than 2 and weakly inhibits Rab geranylgeranyl transferase (RGGT), selectively preventing prenylation ...
Palmer Andreas M - - 2010
Potassium-competitive acid blockers (P-CABs) constitute a new therapeutic option for the treatment of acid-related diseases that are widespread and constitute a significant economical burden. Enantiomerically pure tetrahydrochromenoimidazoles were prepared using the readily available candidate 4 (BYK 405879) as starting material or the Noyori asymmetric reduction of ketones as key reaction. ...
Wang Jinxin - - 2010
Gambogic acid (GA) has been reported to be a potent apoptosis inducer. The fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anticancer agents. We firstly reported the synthesis of gambogellic acid, which was generated under acid catalysis from readily available GA ...
Pan Yan - - 2010
ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (CA) has been widely cultivated as a vegetable or spice in China, Southeast Asia, India, Sri Lanka, Africa, and Oceanic countries and traditionally used for wound healing and maintaining normal blood pressure. AIM OF THE STUDY: The present study was carried out to examine the potential ...
Bennett Stuart N L - - 2010
A series of carboxylic acid glycogen phosphorylase inhibitors, which have potential as oral antidiabetic agents, is described. Defining and applying simple physicochemical design criteria was used to assess the opportunity and to focus synthetic efforts on compounds with the greatest probability of success. The study led to compound 17, which ...
Zheng Chang-Ji - - 2010
Bacterial enoyl-ACP reductase (FabI) has been demonstrated to be a novel antibacterial target. In the course of our screening for FabI inhibitors we isolated two methyl-branched fatty acids from Streptomyces sp. A251. They were identified as 14-methyl-9(Z)-pentadecenoic acid and 15-methyl-9(Z)-hexadecenoic acid by MS and NMR spectral data. These compounds inhibited ...
Kieser Karen J - - 2010
Selective estrogen receptor (ER) down-regulators (SERDs) reduce ERalpha protein levels as well as block ER activity and therefore are promising therapeutic agents for the treatment of hormone refractory breast cancer. Starting with the triarylethylene acrylic acid SERD 4, we have investigated how alterations in both the ligand core structure and ...
Colucci John - - 2010
The discovery of a highly potent and selective EP(4) antagonist MF-766 is discussed. This N-benzyl indole derivative exhibits good pharmacokinetic profile and unprecedented in vivo potency in the rat AIA model.
Bridoux Alexandre - - 2010
Novel thyroxine analogs with hindered phenol, amino and carboxylic acid groups have been synthesized and the effects of the synthesized compounds on angiogenesis using the chick chorioallantoic membrane and mouse matrigel models have been tested. Pharmacological profiles revealed that thyroxine tolerates numerous modifications on the amino group and remains active. ...
Fatmawati Sri - - 2010
CHCl(3) extract of the fruiting body of Ganoderma lucidum was found to show inhibitory activity on human aldose reductase in vitro. From the acidic fraction, potent human aldose reductase inhibitors, ganoderic acid C2 (1) and ganoderenic acid A (2), were isolated together with three related compounds. It was found that ...
Schmidt Darby - - 2010
Niacin is an effective drug for raising HDL cholesterol. However, niacin must be taken in large doses and significant side effects are often observed, including facial flushing, loss of glucose tolerance, and liver toxicity. An anthranilic acid was identified as an agonist of the niacin receptor. In order to improve ...
Fritzson Ingela - - 2010
A strategy that combines virtual screening and structure-guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of ...
Papahatjis Demetris P - - 2010
Two novel methyl-substituted arachidonic acid derivatives were prepared in an enantioselective manner from commercially available chiral building blocks, and were found to be excellent templates for the development of (13S)-methyl-substituted anandamide analogues. One of the compounds synthesized, namely, (13S,5Z,8Z,11Z,14Z)-13-methyl-eicosa-5,8,11,14-tetraenoic acid N-(2-hydroxyethyl)amide, is an endocannabinoid analogue with remarkably high affinity for ...
Albers Harald M H G - - 2010
Autotaxin (ATX) is a secreted nucleotide pyrophosphatase/phosphodiesterase that functions as a lysophospholipase D to produce the lipid mediator lysophosphatidic acid (LPA), a mitogen, chemoattractant, and survival factor for many cell types. The ATX-LPA signaling axis has been implicated in angiogenesis, chronic inflammation, fibrotic diseases and tumor progression, making this system ...
Ciocoiu Calin C - - 2010
Ten 1,4-disubstituted 1,2,3-triazoles 2a-2j were prepared and tested for their ability to increase oleic acid oxidation in human myotubes using a high-throughput multiwell assay. Compounds 2e (2-{4-[(1-(3-fluoro-4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methylthio]-2-methylphenoxy}acetic acid) and 2i (2-{4-[(1-(3-chloro-4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methylthio]-2-methylphenoxy}acetic acid) exhibited potent agonist activities. Compounds 2e and 2i also exhibited powerful agonist effects for both PPARalpha and PPARdelta ...
Usai Igor - - 2010
A click-chemistry-based synthesis of biologically active doxycycline-amino acid conjugates is described. Starting from 9-aminodoxycycline derivatives and complementary functionalized amino acids, ligation was accomplished by copper(I)-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC). The final products were tested in a variety of TetR and revTetR systems, and the C-terminally linked phenylalanine conjugate 12 c ...
Tagad Harichandra D - - 2010
We previously reported potent BACE1 inhibitors KMI-420 and KMI-570 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Acidic moieties at the P(1)(') and P(4) positions of KMI inhibitors are thought to be unfavorable in terms of membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the ...
Ding Wei - - 2010
Azinomycin B is a potent antitumor antibiotic that features a set of unusual, densely assembled functionalities. Among them, the 3-methoxy-5-methylnaphthoic acid (NPA) moiety provides an important noncovalent association with DNA, and may, therefore, contribute to the specificity of DNA alkylation for biological activity exhibition. We have previously cloned and sequenced ...
Zhu Yongqiang - - 2010
A series of novel dipeptidyl boronic acid proteasome inhibitors composed of beta-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i was the most active. The IC(50) value of its pure enantiomer 4q was ...
El-Gendy Nashwa - - 2010
Aerosolized contrast agents may improve the resolution of biomedical imaging modalities and enable more accurate diagnosis of lung diseases. Many iodinated compounds, such as diatrizoic acid, have been shown to be safe and useful for radiographic examination of the airways. Formulations of such compounds must be improved in order to ...
Najar I A - - 2010
In the present investigation 16 phytoconstituents, which are active moieties found in several medicinal herbs, have been evaluated for their P-glycoprotein (P-gp) stimulation/inhibition profiles using a P-gp-dependent ATPase assay in rat jejunal membrane (in vitro). Acteoside, agnuside, catechin, chlorogenic acid, picroside -II and santonin showed an inhibitory effect. Negundoside, picroside ...
Zheng Chang-Ji - - 2010
Aceriphyllum rossii Engler (Saxifragaceae) have been used as a nutritious food in Korea. We found that the methanol extract of A. rossii root and its components, aceriphyllic acid A and 3-oxoolean-12-en-27-oic acid, potently inhibited the growth of the key cariogenic bacteria, Streptococcus mutans, with MIC of 2 to 4 microg/mL. ...
Cheng Keguang - - 2010
Recently, oleanolic acid was found to be an inhibitor of glycogen phosphorylase. For further structural modification, we have synthesized several dimers of oleanolic acid by using amide, ester, or triazole linkage with click chemistry. The click chemistry was shown to be the most efficient method for the dimer synthesis. Nearly ...
von Schacky Clemens - - 2010
Sudden cardiac death (SCD) is an unresolved health issue, and responsible for 15% of all deaths in Western countries. Epidemiologic evidence, as well as evidence from clinical trials, indicates that increasing intake and high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect from SCD and other major adverse ...
Wilson Steven Ray - - 2010
The effect of acid treatment of cyclopamine, a natural antagonist of the hedgehog (Hh) signaling pathway and a potential anti-cancer drug, has been studied. Previous reports have shown that under acidic conditions, as in the stomach, cyclopamine is less effective. Also, it has been stated that cyclopamine converts to veratramine, ...
Murigi Francis N - - 2010
The conformationally constrained tyrosine analogues, (R)- and (S)-5-hydroxy-2-aminoindan-2-carboxylic acids, were prepared by chromatographic separation of diastereomeric dipeptide derivatives formed from N-Boc-L-phenylalanine. Absolute configurations were assigned by X-ray crystallographic analysis.
Sarhan Abdelwareth A O - - 2010
3-aminothiazolo[3,2-a]benzimidazole-2-carbonitrile (2) was prepared and upon hydrolysis using concentrated sulfuric acid or phosphoric acid resulted in the corresponding 3-aminothiazolo[3,2-a]benzimidazole-2-carboxamide derivative (3). Cyclization of the 2 using acetic anhydride or formic acid gave the corresponding pyrimido[4',5':4,5]thiazolo[3,2-a]benzimidazol-4(3H)-one (5) in good yields. Acetylation of 2 with acetic anhydride in pyridine afforded N-acetylaminothiazolo[3,2-a]benzimidazole-2-carbonitrile (6). ...
Faust Mark R - - 2010
In this study azetidine derivatives representing conformationally constrained GABA or beta-alanine analogs were evaluated for their potency as GABA-uptake inhibitors. The study comprised derivatives substituted in 2- as well as in 3-position with either an acetic acid moiety or a carboxylic acid function. In addition, azetidine derivatives bearing a tetrazole ...
Yu Gang - - 2010
A new group of acetic acid (7a-c, R(1) = H), and propionic acid (7d-f, R(1) = Me), regioisomers wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety is attached via its C-3, C-4, and C-5 position was synthesized. This group of compounds exhibited a more potent inhibition, and hence selectivity, for the cyclooxygenase-2 (COX-2) relative ...
Janser Romy F J - - 2010
A series of ethacrynic acid analogues, lacking the alpha,beta-unsaturated carbonyl unit, was synthesized and subsequently evaluated for their ability to inhibit the migration of human breast cancer cells, MCF-7/AZ. Several of the analogues were already active in the low micromolar range, whereas ethacrynic acid itself shows no potential to inhibit ...
Grimstrup Marie - - 2010
The SAR features have been further explored for (2-benzhydryl-4-phenyl-thiazol-5-yl)acetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. The introduction of a nitrogen or a methyl substituent in the benzhydrylic position offer two alternative drugable scaffolds attractive for unsymmetrically substituted derivatives. An imidazole analogue lacks activity due to ...
Chae Su Young - - 2010
Improved glucagon-like peptide-1 (GLP-1) receptor activation is considered one of the most effective targets for antidiabetic therapy. For this purpose, we modified the GLP-1 analog of exendin-4 using two fatty acids (FA) either lauric acid (LUA, C12) or palmitic acid (PAA, C16) at its two lysine residues, to produce; Lys(12)-FA-Exendin-4 ...
Singh Ramendra K - - 2010
Curcumin bioconjugates, viz. di-O-tryptophanylphenylalanine curcumin (2), di-O-decanoyl curcumin (3), di-O-pamitoyl curcumin (4), di-O-bis-(gamma,gamma)folyl curcumin (6), C(4)-ethyl-O-gamma-folyl curcumin (8) and 4-O-ethyl-O-gamma-folyl curcumin (10) have been synthesized and tested for their antibacterial and antiviral activities. The conjugates 2, 3, 4, 6 and 8 have shown very promising antibacterial activity with MIC ranging ...
Genet Cédric - - 2010
We describe here the biological screening of a collection of natural occurring triterpenoids against the G protein-coupled receptor TGR5, known to be activated by bile acids and which mediates some important cell functions. This work revealed that betulinic (1), oleanolic (2), and ursolic acid (3) exhibited TGR5 agonist activity in ...
Koukoulitsa Catherine - - 2010
Aldose reductase (ALR2) of the polyol metabolic pathway is a target enzyme for the treatment of diabetic complications. A variety of synthetic and natural compounds have been observed to inhibit aldose reductase. Among them, rosmarinic acid has been shown to be in vitro an aldose reductase inhibitor in a micromolar ...
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