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1.
Zinc, magnesium, aluminum and copper complexes of several potent, clinically used carbonic anhydrase (CA) sulfonamide inhibitors, such as acetazolamide, methazolamide, ethoxzolamide and benzolamide were tested for their possible applications as antacids, in experimental animals. Gastric acid secretion parameters 3 days after treatment with these CA inhibitors (2 x 500 mg, twice a day), in dogs with chronic gastric fistulas, led to the observation that the gastric acid parameters BAO (the basal acid output), and MAO (the maximal acid output after stimulation with histamine) were drastically reduced, as compared to the same parameters in animals that did not receive these enzyme inhibitors. These are promising results for the possible use of metal complexes of heterocyclic sulfonamides as treatment alternatives (alone or in combination with other drugs) for gastric acid secretion imbalances. 相似文献
2.
Rami M Cecchi A Montero JL Innocenti A Vullo D Scozzafava A Winum JY Supuran CT 《ChemMedChem》2008,3(11):1780-1788
The synthesis and carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of two series of aromatic sulfonamides and their Cu(II) derivatives, incorporating metal-complexing moieties of the DTPA, DOTA, and TETA type are reported. The new compounds were designed in such a way as to possess high affinity for Cu(II) ions, exploiting four pendant carboxylate moieties in the DTPA derivatives, as well as the cyclen/cyclam macrocyles, and three pendant acetate moieties in the DOTA and TETA derivatives. The new derivatives showed modest inhibition of the cytosolic isoform CA I (K(I) values in the range of 66-2130 nM), were better CA II inhibitors (K(I) values in the range of 21-360 nM), and excellent inhibitors of the tumor-associated isoform CA IX (K(I) values in the range of 4.1-110 nM), with selectivity ratios for the inhibition of the tumor (CA IX) over the cytosolic (CA II) isozyme in the range of 10.74-20.88 for the best derivatives. Copper complexes were more inhibitory than the corresponding ligand sulfonamides, and showed membrane impermeability, thus, having the possibility to specifically target the transmembrane CA IX that has an extracellular active site. Incorporation of radioactive copper isotopes in this type of CA inhibitor may lead to interesting diagnostic/therapeutic applications for such compounds. 相似文献
3.
Indanesulfonamides are interesting lead compounds for designing selective inhibitors of the different isoforms of the zinc enzyme Carbonic Anhydrase (CA). Herein, we report for the first time the X-ray crystal structure of two such derivatives, namely indane-5-sulfonamide and indane-2-valproylamido-5-sulfonamide, in complex with the physiologically dominant human isoform II. The structural analysis reveals that, although these two inhibitors have quite similar chemical structures, the arrangement of their indane ring within the enzyme active site is significantly diverse. Thus, our findings suggest that the introduction of bulky substituents on the indane-sulfonamide ring may alter the binding mode of this potent class of CA inhibitors, although retaining good inhibitory properties. Accordingly, the introduction of bulky tail moieties on the indane-sulfonamide scaffold may represent a powerful strategy to induce a desired physicochemical property to an aromatic sulfonamide or to obtain inhibitors with diverse inhibition profiles and selectivity for various mammalian CAs. 相似文献
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Three heterocyclic compounds namely 3-anilino-5-imino-4-phenyl-1, 2,4-thiadiazoline (AIPT), 3-anilino-5-imino-4-tolyl-1, 2,4-thiadiazoline (AITT), and 3-anilino-5-imino-4-chlorophenyl-1, 2,4-thiadiazoline (AICT) were synthesized and their influence on the inhibition of corrosion of mild steel in 1 M HCl and 0.5 M H2SO4 was investigated by weight loss and potentiodynamic polarization techniques. The values of activation energy and free energy of adsorption of these compounds were also calculated. Potentiodynamic polarization studies were carried out at room temperature, and showed that all the compounds were mixed type inhibitors causing blocking of active sites on the metal. The inhibition efficiency of the compounds was found to vary with concentration, temperature and immersion time. Good inhibition efficiency was evidenced in both acid solutions. The adsorption of the compounds on mild steel for both acids was found to obey the Langmuir adsorption isotherm. Electrochemical impedance spectroscopy was also used to investigate the mechanism of corrosion inhibition. 相似文献
6.
Complexes containing the anions of 5-benzoylamido-1,3,4-thiadiazole-2-sulfonamide and 5-(3-nitro-benzoylamido)-1,3,4-thiadiazole-2-sulfonamid as ligands, and V(IV); Cr(III); Fe(III); Co(II); Ni(II); Cu(II) and Ag(I) were synthesized and characterized by standard procedures (elemental analysis; IR, electronic, and EPR spectroscopy; TG, magnetic and conductimetric measurements). The original sulfonamides and their metal complexes are strong inhibitors of two carbonic anhydrase (CA) isozymes, CA I and II. 相似文献
7.
Supuran CT 《Metal-Based Drugs》1996,3(2):79-83
Complexes of the diuretic benzothiadiazine derivative chlorothiazide (6-chloro-7-sulfamoyl- 1,2,4-benzothiadiazine-1,1-dioxide) with V(IV); Fe(II); Co(II); Ni(II); Cu(II), Ag(I) and U(VI) were prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and conductimetric measurements. The complexes behave as effective inhibitors for two isozymes (I and II) of carbonic anhydrase (CA). 相似文献
8.
Fort S Varrot A Schülein M Cottaz S Driguez H Davies GJ 《Chembiochem : a European journal of chemical biology》2001,2(5):319-325
A new class of inhibitors for beta-D-glycoside hydrolases, in which a single alpha-(1-->4)-glycosidic bond is incorporated into an otherwise all-beta-(1-->4)-linked oligosaccharide, is described. Such mixed beta/alpha-linkage cellooligosaccharides are not transition-state mimics, but instead are capable of utilising binding energy from numerous subsites, spanning either side of the catalytic centre, without the need for substrate distortion. This binding is significant; a mixed alpha/beta-D-tetrasaccharide acts competitively on a number of cellulases, displaying inhibition constants in the range of 40-300 microM. Using the Bacillus agaradhaerens enzyme Cel5A as a model system, one such mixed beta/alpha-cellooligosaccharide, methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside, displays a K(i) value of 100 microM, an inhibition at least 150 times better than is observed with an equivalent all-beta-linked compound. The three-dimensional structure of B. agaradhaerens Cel5A in complex with methyl 4(II),4(III)-dithio-alpha-cellobiosyl-(1-->4)-beta-cellobioside has been determined at 1.8 A resolution. This confirms the expected mode of binding in which the ligand, with all four pyranosides in the (4)C(1) chair conformation, occupies the -3, -2 and +1 subsites whilst evading the catalytic (-1) subsite. Such "by-pass" compounds offer great scope for the development of a new class of beta-D-glycoside hydrolase inhibitors. 相似文献
9.
Osmium carbonyl clusters, especially the cluster [Os(3)(CO)(10)(NCCH(3))(2)], were found to be active against four cancer cell lines, namely, ER+ breast carcinoma (MCF-7), ER- breast carcinoma (MDA-MB-231), metastatic colorectal adenocarcinoma (SW620), and hepatocarcinoma (Hep G2). The mode of action was studied in MCF-7 and MDA-MB-231 cell lines by a number of morphological and apoptosis assays, all of which pointed to the induction of apoptosis. 相似文献
10.
Schulz F Gelhaus C Degel B Vicik R Heppner S Breuning A Leippe M Gut J Rosenthal PJ Schirmeister T 《ChemMedChem》2007,2(8):1214-1224
A broad protease-based and cell-based screening of protease inhibitors yielded the aziridine-2-carboxylic acid derivative 2 a and the N-acylated aziridine-2,3-dicarboxylic acid derivatives 32 a and 34 b as the most potent inhibitors of falcipain-2 and falcipain-3 (IC(50) falcipain-2: 0.079-5.4 microM, falcipain-3: 0.25-39.8 microM). As the compounds also display in vitro activity against the P. falciparum parasite in the submicromolar and low micromolar range, these compound classes are leads for new antiplasmodial falcipain inhibitors. 相似文献
11.
Complexes containing five 4,5-disubstituted-3-mercapto-1,2,4-triazoles and Zn(II), Hg(II) and Cu(I) were synthesized and characterized by standard procedures (elemental analysis; IR, electronic and NMR spectroscopy, conductimetry and TG analysis). Both the thione as well as the thiolate forms of the ligands were evidenced to interact with the metal ions in the prepared complexes. The original mercaptans and their metal complexes behave as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II and IV, but did not lower intraocular pressure in rabbits in animal models of glaucoma. 相似文献
12.
Gupta RC Nautiyal P Jhingran AG Kamboj VP Setty BS Anand N 《Indian journal of chemistry》1981,(4):303-307
The results of a screening program to test the spermicidal effectiveness of several compounds is presented. The program was initiated after N-substituted 3-aminoacrylophenones were found to have unexpected spermicidal activity. The compounds had been synthesized as possible antiinflammatory agents. This result prompted the synthesis and screening of N-substituted alpha-aminomethylacrylophenones, alpha-(2-aminomethyl)acrylophenones and 3-N-substituted-2-methyleneindan-1-ones. The starting materials, substituted acetophenones, for the synthesis of N-substituted alpha-aminomethylacrylophenones were either commercial products or obtained by standard methods. N-substituted amino-butyrophenone was reacted with paraformaldehyde to yield the alpha-(2 aminoethyl)acrylophenones. A series of reactions was undertaken to synthesize 2-methyleneindan-1-ones. The preparation of each is detailed and molecular formulas are provided. Spermicidal activity was assessed by dissolving the compound in physiological saline at different concentrations. 2 drops of rat sperm suspension or human semen were placed on a slide, followed by 2 drops of a compound solution. Control slides of physiological saline were prepared. The contents were mixed for approximately 5 seconds and examined under a phase contrast microscope. The results were considered positive if 100% of the spermatozoa became immotile instantaneously. Several of the compounds showed marked spermicidal activity. 相似文献
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15.
A. Braig 《Progress in Organic Coatings》1997,34(1-4)
Amine and transition metal based complexes with 4-methyl-γ-oxo-benzene-butanoic acid represent a new class of corrosion inhibitors specifically designed for long-term corrosion protection in waterborne coatings. Today, corrosion protection in waterborne technology is typically achieved using traditional anticorrosive pigments initially developed for use in solventborne coatings. Regulations concerning heavy metals and limitations regarding the compatibility and performance of such materials in waterborne coatings have created a need for novel approaches. Mechanistic aspects are discussed for the 4-methyl-γ-oxo-benzene-butanoic complexes based on electrochemical solution experiments (electrochemical impedance spectroscopy (EIS), linear sweep voltammetry (LSV)) and investigations performed on coated substrates. Exposure results underline the high efficiency of such complexes for both long-term corrosion protection and weld seam rust control in waterborne coatings. 相似文献
16.
Terpyridine-manganese complexes: A new class of bleach catalysts for detergent applications 总被引:1,自引:0,他引:1
Oxidation catalysis is one approach used to improve the performance of hydrogen peroxide in laundry bleach applications. We
introduce herein a new class of bleach catalysts based on the ligand 2,2′∶6′,2″ terpyridine. A set of manganese complexes
of substituted terpyridines was investigated with respect to their physicochemical properties and bleach performance. Introduction
of electron-donating hydroxy and amine substituents in the 4-position of the individual pyridine rings improves the bleach
performance in model experiments with morin (2′,3,4′,5,7-pentahydroxyflavone) in solution as well as on tea-stained cotton
fabrics. All the catalysts show excellent bleach performance at 40 and 25°C under European washing conditions. Performance
is superior to that of the activator tetraacetyl ethylenediamine (TAED) but depends critically on the substitution pattern.
Dye damage caused by the catalysts is similar to that of TAED, proving that catalytic bleach systems with high performance
and low damage are indeed feasible. Model experiments revealed that the complexes are highly stable under aqueous alkaline
conditions in the presence of hydrogen peroxide. The optimal pH for catalytic activity is about 10. For a catalyst to have
a high bleach performance, it must possess a sufficiently low activity to catalyze disproportionation of hydrogen peroxide,
which is a major side reaction of catalytic bleach with manganese complexes. All the catalysts showed a similar affinity for
the cotton fabric, suggesting that differences in bleach activity of complexes are not caused by differences in the fabric
affinity. 相似文献
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18.
Pyromellitic tetranitrile and 4,4′-diaminodiphenyl ether have been reacted in solution and in the solid state, and the macrocyclic polymer produced by each method of reaction has been shown to be structurally identical. Other macrocyclic polymers have been prepared by the solid state reactions of a number of aromatic diamines and pyromellitic tetranitrile. The diamines were selected to provide variations in the size of the macrocycle and in the level of strain within the ring. Preliminary studies suggest that these variations have an observable effect upon the ease of macrocyclization, but no marked influence upon the thermal stability of the polymers. 相似文献
19.
Botta M Distrutti E Mencarelli A Parlato MC Raffi F Cipriani S Fiorucci S 《ChemMedChem》2008,3(10):1580-1588
Nitric oxide (NO) is a gaseous mediator that exerts key regulatory functions in mammalian cells. Low levels of NO exert homeostatic functions and counteract inflammation, whereas high amounts of NO cause tissue destruction and cellular death. Herein we describe a new class of nitric oxide synthase (NOS) inhibitor NO-donating drugs (NI-NODs). Human endothelial cells and human monocyte-based activity screening showed that NI-NODs inhibit IL-1beta production, modulate PGE(2) production, and protect against apoptosis. In a rodent model of colitis, NI-NOD1 and NI-NOD2 potently decreased inflammation. These data show that NI-NODs are effective in both in vitro and in vivo models of inflammation, mimicking the positive effects of low levels of NO and suppressing NOS-induced NO production. 相似文献