Inhibition of 6-hydroxydopamine-induced oxidative damage by 4,5-dihydro-3H-2-benzazepine N-oxides

A number of new analogs of 3,3-dimethyl-4,5-dihydro-3H-2-benzazepine 2-oxide, structurally related to the nitrone spin trap α-phenyl-N-tert-butylnitrone (PBN), were synthesized and evaluated for their activity in vitro as protectants against oxidative stress induced in rat brain mitochondria by 6-hydroxydopamine (6-OHDA), a neurotoxin producing experimental model of Parkinson's disease (PD). As assessed by a fluorimetric assay, all 2-benzazepine-based nitrones were shown to decrease hydroxyl radicals (radical dotOH) generated during 6-OHDA autoxidation. The inhibition effects on the radical dotOH formation shown by the 5-gem-dimethyl derivatives, 2–4 times higher than those of the corresponding 5-methyl derivatives, were attributed to the flattening effect of the 5-gem-dimethyl group on the azepine ring, which should enhance nitrone reactivity and/or increase stability of the radical adducts. In contrast, owing to steric hindrance, a methyl group to C-1 diminishes the radical dotOH-scavenging activity of the nitrone group. All the assayed compounds were more potent than PBN as inhibitors of 6-OHDA-induced lipid peroxidation (LPO) and protein carbonylation (PCO), taken as an indicator of mitochondrial protein oxidative damage. The most promising antioxidant (compound 11), bearing 5-gem-dimethyl and spiro C-3 cyclohexyl groups, highlighted in this study as the best features, inhibited LPO and PCO with IC50 values of 20 and 48 μM, respectively, showing a potency improvement over PBN of two order magnitude. Both LPO and PCO inhibition potency data were found primarily related to the radical dotOH-scavenging activities, whereas lipophilicity plays a role in improving the LPO (but not PCO) inhibition, as a statistically valuable two-parameter equation proved.The Spanish authors thank the Ministerio de Educación y Ciencia and the Europe Regional Development Fund (Madrid, Spain, Grants BFI2003-00493 and SAF2007-66114) for financial support. The Italian authors thank the Italian Ministry for Education Universities and Research (MIUR, Rome, Italy; PRIN 2004, Grant No. 2004037521_006) for financial support.S

Three-Component Reaction of 3-Arylidene-3H-Indolium Salts, Isocyanides, and Alcohols

A novel isocyanide-based multicomponent synthesis of alkyl aryl(indol-3-yl)acetimidates has been established. Starting from aryl(indol-3-yl)methylium tetrafluoroborates, aromatic isocyanides and alcohols, the imidates were obtained in moderate to very good yields. Consecutive four-component synthesis of the above mentioned imidates from N-alkylindoles, aromatic aldehydes, aromatic isocyanides and alcohols was also proposed. In addition, it was shown that in the presence of water, aryl(indol-3-yl)methylium tetrafluoroborates reacted with isocyanides to furnish aryl(indol-3-yl)acetamides

Prediction of thermomagnetic and thermoelectric properties for novel materials and systems

We express the link between conductivity and coefficients of Seebeck, Nernst-Ettingshausen, Peltier, and Thompson and Reghi-Leduc via the temperature derivative of the chemical potential of a system. These general expressions are applied to three-, two- and one-dimensional systems of charge carriers having a parabolic or Dirac spectrum. The method allows for predicting thermoelectric and thermomagnetic properties of novel materials and systems

The formation of hydrogels based on chitosan and its water-soluble derivatives

This review considers articles on the formation of hydrogels based on chitosan as well as succinylated and quaternized chitosan derivatives. They are synthesized using low toxicity reagents, under ordinary conditions (low production costs). Chitosan derivatives are soluble in an extended range of pH values and characterized by mucoadhesiveness, bioavailability and biodegradability, which extends the potential of their medical applications. One of the most important properties of chitosan and its derivatives is the ability to form hydrogels. Depending on the nature of the bonds that occur during formation, hydrogels are divided into chemically or physically crosslinked, or a mixture of the two. Chemically crosslinked gels have covalent bonds, while physically crosslinked gels are formed by noncovalent interactions, for example, ionic. Mixed hydrogels have both types of crosslinking

DBU-Catalyzed Alkyne-Imidate Cyclization toward 1-Alkoxypyrazino[1,2-a]indole Synthesis

1-(Propargyl)indol-2-carbonitriles react with alcohols to afford 1-alkoxypyrazino[1,2- a]indoles under DBU-catalyzed microwave-assisted conditions. The reaction scope includes a wide range of indoles, primary and secondary alcohols, and a thiol. The initial mechanistic study shows that the domino process presumably proceeds through an alkyne-allene rearrangement, imidate formation, and nucleophilic cyclization reaction sequence.status: publishe

Microwave-Assisted Synthesis of Fluorescent Pyrido[2,3-b]indolizines from Alkylpyridinium Salts and Enaminones

Pyridinium ylides are well recognized as dipoles for cycloaddition reactions. In its turn, the microwave-assisted interaction of N-(cyanomethyl)-2-alkylpyridinium salts with enaminones unexpectedly proceeds as a domino sequence of cycloisomerization and cyclocondensation reactions, instead of a 1,3-dipolar cycloaddition. The reaction takes place in the presence of sodium acetate as base and employs benign solvents. The optical properties of the resulting pyrido[2,3-b]indolizines were studied, showing green light emission with high fluorescence quantum yields

Microwave-Assisted Synthesis of Fluorescent Pyrido[2,3-b]indolizines from Alkylpyridinium Salts and Enaminones

Pyridinium ylides are well recognized as dipoles for cycloaddition reactions. In its turn, the microwave-assisted interaction of N-(cyanomethyl)-2-alkylpyridinium salts with enaminones unexpectedly proceeds as a domino sequence of cycloisomerization and cyclocondensation reactions, instead of a 1,3-dipolar cycloaddition. The reaction takes place in the presence of sodium acetate as base and employs benign solvents. The optical properties of the resulting pyrido[2,3-b]indolizines were studied, showing green light emission with high fluorescence quantum yields.status: publishe

Photoredox-Catalyzed Hydrosulfonylation of Arylallenes

(Het)Arylallenes undergo hydrosulfonylation under photoredox-catalyzed conditions. The reaction gives vinyl sulfones in a regio- and diastereoselective manner, employing sodium sulfinates as the sulfonyl source and eosin Y as the photocatalyst. Indol-1-yl, pyrrol-1-yl, phenyl, and naphtylallenes might be used. Aliphatic allenes are incompatible with the reaction conditions.status: publishe