Carbonic anhydrase inhibitors: design of spin-labeled sulfonamides incorporating TEMPO moieties as probes for cytosolic or transmembrane isozymes.

A series of spin-labeled sulfonamides incorporating TEMPO moieties were synthesized by a procedure involving the formation of a thiourea functionality between the benzenesulfonamide and free radical fragment of the molecules. The new compounds were tested as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.

Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols.

Inhibition of the newest isoform of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors: bioreductive nitro-containing sulfonamides with selectivity for targeting the tumor associated isoforms IX and XII.

2-Substituted-5-nitro-benzenesulfonamides incorporating a large variety of secondary/tertiary amines were explored as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors. Part 91. Metal complexes of heterocyclic sulfonamides as potential pharmacological agents in the treatment of gastric Acid secretion imbalances.

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.

Functionalized Derivatives of Benzo-Crown Ethers. Part 4. Antifungal Macrocyclic Supramolecular Complexes of Transition Metal Ions Acting as Lanosterol-14-alpha-Demethylase Ihibitors.

Poly- and mononuclear metal complexes of 2,3,11,12-bis[4-(10-aminodecylcarbonyl)]benzo-18- crown-6 (L) and Cu(II); Ni(II); Co(II) and Cr(III) have been synthesized and characterized by standard physico-chemical procedures. In the newly prepared complexes the crown moiety oxygen atoms of the macrocyclic host did not generally interact with metal ions, whereas the two amino groups of the ligand always did. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp.

Carbonic Anhydrase Inhibitors Part 72 Synthesis and Antiglaucoma Properties of Metal Complexes of p-Fluorobenzolamide.

Metal complexes of a heterocyclic sulfonamides possessing very strong carbonic anhydrase (CA) inhibitory properties, i.e., 5-(p-fluorobenzenesulfonylamido)-1,3,4-thiadiazole-2-sulfonamide (p-fluorobenzolamide) were prepared.

Synthesis and antifungal activity of metal complexes containing dichloro-tetramorpholino-cyclophosphazatriene.

Metal complexes of dichloro-tetramorpholino-cyclophosphazatriene containing divalent cations such as Ni(II), Co(II), and Mn(II) have been prepared and characterised by standard physico-chemical procedures (elemental chemical analysis, IR and UV-VIS spectra, conductimetric measurement). The newly synthesised compounds possessed antifungal activity against Aspergillus and Candida spp., some of them showing effects comparable to ketoconazole (with minimum inhibitory concentrations in the range of 2- 30 mug/mL) but being generally less active as compared to the azole.

Carbonic Anhydrase Inhibitors. Part 55 Metal Complexes of 1,3,4-Thiadiazole-2-Sulfonamide Derivatives: In Vitro Inhibition Studies With Carbonic Anhydrase Isozymes I, II and IV.

Coordination compounds of 5-chloroacetamido-1,3,4-thiadiazole-2-sulfonamide (Hcaz) with V(IV), Cr(lll), Fe(ll), Co(ll), Ni(ll) and Cu(ll) have been prepared and characterized by standard procedures (spectroscopic, magnetic, EPR, thermogravimetric and conductimetric measurements). Some of these compounds showed very good in vitro inhibitory properties against three physiologically relevant carbonic anhydrase (CA)isozymes, i.e.

Complexes with biologically active ligands. Part 11. Synthesis and carbonic anhydrase inhibitory activity of metal complexes of 4,5-disubstituted-3-mercapto-1,2,4-triazole derivatives.

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.

Combined action of a bacterial monooxygenase and a fungal laccase for the biodegradation of mono- and poly-aromatic hydrocarbons.

The combined action of a wide substrate range toluene o-xylene monooxygenase from Pseudomonas sp. OX1, able to convert many aromatic compounds into mono- and di-hydroxylated derivatives, and fungal laccases from Pleurotus ostreatus which oxidize these hydroxylated products yielding polymers with reduced toxicity is described. This strategy permits to overcome many of the substrate specificity problems and dead end toxic products formation generally encountered in complex bacterial biodegradation pathways.

Indanesulfonamides as carbonic anhydrase inhibitors and anticonvulsant agents: structure-activity relationship and pharmacological evaluation.

A small library of indanesulfonamides was screened for the inhibition of the human carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.

Diuretics such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide, and bumetanide containing primary sulfamoyl moieties were reevaluated as inhibitors of 12 human carbonic anhydrases (hCAs, EC 4.2.1.

Biotransformation of chloroaromatics: the impact of bioavailability and substrate specificity.

The effect of surfactants on the biodegradation of mono-aromatic hydrocarbons such as benzene, chlorobenzene and 1,2-dichlorobenzene by an Escherichia coli JMI09(MI) recombinant strain, carrying a gene cluster containing the genes for benzene dioxygenase, cis-benzene dihydrodiol dehydrogenase, and catechol 2,3-dioxygenase from Pseudomonas putida ML2, has been investigated. We observed that the efficiency of the benzene dioxygenase catalyzed conversions to cis-dihydrodiols depends on the balance among real substrate specificity, bioavailability, and toxicity effects of highly concentrated aromatic hydrocarbons. The utilization of non ionic surfactants makes it possible to partly overcome the limiting step of biodegradation processes for scarcely water soluble hydrocarbons hindered by their limited bioavailability.

Carbonic anhydrase inhibitors: the X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors.

Ethoxzolamide, an almost forgotten inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.

Investigations of the esterase, phosphatase, and sulfatase activities of the cytosolic mammalian carbonic anhydrase isoforms I, II, and XIII with 4-nitrophenyl esters as substrates.

The esterase, phosphatase, and sulfatase activities of carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors. Inhibition of the cytosolic and tumor-associated carbonic anhydrase isozymes I, II and IX with some 1,3,4-oxadiazole- and 1,2,4-triazole-thiols.

Novel mercapto-1,3,4-oxadiazole and -1,2,4-triazole derivatives were synthesized by various pathways starting from 4-(4-halogeno-phenylsulfonyl)benzoic acid hydrazides which were reacted with carbon disulfide or isothiocyanates. The heterocyclic mercaptans prepared in this way were assayed as inhibitors of three physiologically relevant isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.

Carbonic anhydrase activation and the drug design.

The activation mechanism of Carbonic Anhydrase was recently explained using kinetic, spectroscopic and X-ray techniques. It has been demonstrated that the activators molecules (CAAs) bind at the entrance of the enzyme active-site facilitating the rate-determining step of CA catalytic cycle. Drug design studies have been performed in order to obtain strong CAAs belonging to several chemical classes: amino acids, azoles, amine and their derivatives, etc.

The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents.

Inhibition of carbonic anhydrase (CA, EC 4.2.1.

Design of zinc binding functions for carbonic anhydrase inhibitors.

Zinc ion plays a crucial role in the protein's functions and is linked to a variety of physiological processes. It constitutes an essential component of numerous enzymes especially carbonic anhydrase (CAs, EC 4.2.

Carbonic anhydrase inhibitors: the very weak inhibitors dithiothreitol, beta-mercaptoethanol, tris(carboxyethyl)phosphine and threitol interfere with the binding of sulfonamides to isozymes II and IX.

The inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase activators: activation of the human tumor-associated isozymes IX and XII with amino acids and amines.

The first activation study of the human carbonic anhydrase (hCA, EC 4.2.1.

Fungal laccase, cellobiose dehydrogenase, and chemical mediators: combined actions for the decolorization of different classes of textile dyes.

Dyes belonging to the mono-, di-, tri- and poly-azo as well as anthraquinonic and mono-azo Cr-complexed classes, chosen among the most utilized in textile applications, were employed for a comparative enzymatic decolorization study using the extracellular crude culture extracts from the white rot fungus Funalia (Trametes) trogii grown on different culture media and activators able to trigger different levels of expression of oxidizing enzymes: laccase and cellobiose dehydrogenase. Laccase containing extracts were capable to decolorize some dyes from all the different classes analyzed, whereas the recalcitrant dyes were subjected to the combined action of laccase and the chemical mediator HBT, or laccase plus cellobiose dehydrogenase. Correlations among the decolorization degree of the various dyes and their electronic and structural diversities were rationalized and discussed.

Carbonic anhydrase inhibitors: inhibition of human cytosolic isozymes I and II and tumor-associated isozymes IX and XII with S-substituted 4-chloro-2-mercapto-5-methyl-benzenesulfonamides.

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.

Carbonic anhydrase inhibitors: interactions of phenols with the 12 catalytically active mammalian isoforms (CA I-XIV).

The inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies.

2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for its interaction with the 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.