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71.
Saczewski J Hudson A Scheinin M Rybczynska A Ma D Saczewski F Laird S Laurila JM Boblewski K Lehmann A Gu J Watts H 《Bioorganic & medicinal chemistry》2012,20(1):108-116
A series of 2-[(heteroaryl)methyl]imidazolines was synthesized and tested for their activities at α(1)- and α(2)-adrenoceptors and imidazoline I(1) and I(2) receptors. The most active 2-[(indazol-1-yl)methyl]imidazolines showed high or moderate affinities for α(1)- and α(2)-adrenoceptors. However, their intrinsic activities at α(2A)-adrenoceptors proved to be negligible. A selected 7-chloro derivative behaved as a potent α(1)-adrenoceptor antagonist and exhibited peripherally mediated hypotensive effects in rats. 相似文献
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73.
Brzozowski Z Saczewski F Sławiński J Bednarski PJ Grünert R Gdaniec M 《Bioorganic & medicinal chemistry》2007,15(7):2560-2572
A new series of N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamides 23-48 have been synthesized as potential anticancer agents. All compounds were screened for their cytotoxic activity against six human tumor cell lines. The selected compounds 23-27, 30, 31, 33, 35, 38, 42, 45, and 46 were further tested at the US National Cancer Institute for their in vitro activities against a panel of 53-59 human tumor cell lines. The compounds 23-26, 30, 31, 33, 38, 42, 45, and 46 showed 50% growth inhibitory activity in low micromolar concentration (GI(50)=0.03-4.9 microM) against one or more human tumor cell lines (Table 3). The prominent compound with remarkable activity (GI(50)=0.03 microM, TGI=1.3 microM) and selectivity toward melanoma UACC-257 cell line was N-(6-chloro-7-cyano-1,1-dioxo-1,4,2-benzodithiazin-3-yl)-N-(phenyl)-5-bromothiophene-2-sulfonamide 46. 相似文献
74.
The work of adhesion between water and a heptane solution of phospholipids extracted from spring (cv. Jara) and winter (cv. Grana) wheat ( Triticum aestivum L.) grown at 2°C and 20°C was measured in order to determine the effect of changes in the composition of fatty acids on the hydrophilic properties of the lipid bilayer of membranes. The work of adhesion water/phospholipids was positively correlated with the contents of the oleic and linoleic acids (18:1 and 18:2, respectively) and negatively correlated with the content of linolenic acid (18:3) in the phospholipids. The sensitivity of the work of adhesion to changes in the particular fatty acids decreased with increasing number of double bonds. In addition, it depended on the genotype and on the temperature of growth of the seedlings. 相似文献
75.
Monika Tarnowska Stanislaw Oldziej Adam Liwo Piotr Kania Franciszek Kasprzykowski Zbigniew Grzonka 《European biophysics journal : EBJ》1992,21(3):217-222
Diazomethyl ketones are one of the most effective irreversible inhibitors of cysteine proteinases and are therefore very important in drug design. In the present study a mechanism of inactivation is proposed based on the results of model MNDO calculations of the possible pathways. It was found that the mercaptide nucleophile, on approaching the carbonyl carbon as in the catalytic reaction path, binds to the inner diazo nitrogen. The intermediate thus formed can rearrange giving a stable product, -thioketone, and molecular nitrogen, with a considerable energy gain. The energy barrier to this process is equal to 36.9 kcal/mol, and corresponds to a pyramidal transition state with the vertex at the methylene carbon and the base formed by the carbonyl, thiol, and diazo groups. The energy barrier can be lowered on deprotonation of the intermediate. Based on the results obtained it was concluded that good irreversible inhibitors of cysteine proteases must fulfil two structural requirements: i) the dimensions and charge distribution must be similar to those of the peptide bond and ii) a second electrophilic center must be present in the neighbourhood of the carbonyl carbon. These are requirements which are satisfied by other strong cysteine proteinase inhibitors: -chloroketones and -ketooxiranes. 相似文献
76.
Eliza Malinowska Wojciech Krzyczkowski Franciszek Herold Grzegorz Łapienis Joanna Ślusarczyk Piotr Suchocki Mieczysław Kuraś Jadwiga Turło 《Enzyme and microbial technology》2009,44(5):334-343
The effects of inorganic selenium (sodium selenite) and Selol containing selenitetriglycerides synthesized from sunflower oil on mycelial growth and selenium-containing extracellular (EPS) and intracellular (IPS) polysaccharides production were examined in shake flask cultures of Hericium erinaceum.Unlike sodium selenite which inhibited mycelial growth, Selol increased in biomass production in a dose-dependent manner. Selol also dramatically enhanced EPS formation to 2.25 g/L which is 2.5–fold higher than in the control. Selenium content in EPS and IPS obtained from Selol-enriched medium reached a maximum of 4.89 and 4.69 mg/g, respectively.The in vitro antioxidant activities of polysaccharides were evaluated by reducing power, inhibition of lipid peroxidation, and 1,1-diphenyl-dipicrylhydrazyl radicals scavenging assays. The selenium-containing EPS showed an excellent antioxidant activity correlated well with increasing concentrations.The results suggested that selenium-containing EPS from H. erinaceum submerged culture should be explored as a novel selenium source in dietary supplements, with potent antioxidant properties. 相似文献
77.
Saczewski F Sławiński J Kornicka A Brzozowski Z Pomarnacka E Innocenti A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry letters》2006,16(18):4846-4851
Some 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones were prepared and investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I and II (cytosolic enzymes), and the tumor-associated CA IX and XII. Some mercaptans led to a consistent increase of inhibitory power (52.8- to 243-fold) over the corresponding oxidized (S-S type) derivatives, acting as potential hypoxia-activatable drugs. 相似文献
78.
Saczewski F Innocenti A Sławiński J Kornicka A Brzozowski Z Pomarnacka E Scozzafava A Temperini C Supuran CT 《Bioorganic & medicinal chemistry》2008,16(7):3933-3940
A series of S-substituted 4-chloro-2-mercapto-5-methyl-benzenesulfonamides has been investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, the cytosolic, ubiquitous isozymes CA I and II, as well as the transmembrane, tumor-associated isozymes CA IX and XII. The new derivatives were inefficient inhibitors of isoform I (K(I)s in the range of 2.7-18.7 microM) but generally had low nanomolar affinity for the inhibition of the other three isoforms (K(I)s in the range of 2.4-214 nM against hCA II; 1.4-47.5 nM against hCA IX, and 1.7-569 nM against hCA XII, respectively). Some selectivity for the inhibition of the tumor-associated versus the cyctosolic isoform II with some of these compounds has also been evidenced. As CA IX is an important marker of tumor hypoxia and its predictive, prognostic, and druggability potentials for designing antitumor therapies were recently validated, detection of selective, potent CA IX inhibitors may be relevant in the fight against cancers overexpressing CA isozymes. 相似文献
79.
Lopot M Ciechanowska M Malewski T Mateusiak K Misztal T Przekop F 《Reproductive biology》2008,8(2):149-161
80.
Burdan F 《Birth defects research. Part B, Developmental and reproductive toxicology》2004,71(5):321-330
BACKGROUND: Ibuprofen and tolmetin are popular non-steroidal anti-inflammatory drugs. Previous animal studies taken with single daily doses showed their good prenatal tolerability. However, since both cyclooxygenase (COX) inhibitors have a short half-life, the current report presents drug developmental effects after triple daily doses administration, as they are used in human. METHODS: Drugs were separately, orally dosed to pregnant rats triple daily 8 hr apart from day 8 to 21 (GD=1-plug day). The total daily doses were set at 25.5, 255.0, and 600.0 mg/kg for ibuprofen and 25.5, 255.0, and 2550.0 mg/kg for tolmetin. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. RESULTS: Maternal toxicity and intrauterine growth retardation were found in groups exposed to the highest doses of both drugs. An increase of external variations was reported in groups exposed to the middle and highest dose of ibuprofen and to the highest dose of tolmetin. Skeletal variations were significantly different only in litters treated with the highest doses of the drugs. Pooled statistical analysis showed a higher incidence of midline and ventricular septal (VSD) defect in rat fetuses exposed to COX inhibitors when compared with historical control data. For ibuprofen, the influence on VSD was similar to aspirin. CONCLUSION: Both COX inhibitors were toxic to dams in the highest doses evaluated, which caused a significantly greater incidence of intrauterine growth retardation and developmental variations. 相似文献