Enzo Cadoni

Supercritical CO2 extraction of lycopene and β-carotene from ripe tomatoes

Abstract This work describes the influence of some operative parameters of supercritical carbon dioxide extraction employed for the isolation of lycopene and β-carotene from the pulp and skins of ripe tomatoes. The extractions were conducted at pressures and temperatures ranging from 2500 to 4000 psi and 40 to 80°C, respectively. The extracted product at 4000 psi and 80°C contained about 65% of lycopene and 35% of β-carotene. Lycopene and β-carotene showed a different solubility in the supercritical fluid depending on process parameters. With a proper choice of operative parameters, it has been possible to obtain a product that contained 87% lycopene and 13% β-carotene.

Dyeing polyester fibres with disperse dyes in supercritical CO2

Abstract The isothermal sorption of a series of thiadiazolyl azo dyes to be used as disperse dyes for polyester fibres has been carried out using supercritical CO2 as the dyeing medium. The experiments were recorded at temperatures from 80 to 120°C and pressures from 2500 to 4000 psi. The results obtained in supercritical CO2 were compared with those of traditional dyeing in water. The study showed that the disperse dyes used generally exhibited high substantivity towards PET fibres and excellent fastness and, that the extent of dye absorbed by the fibre in supercritical fluid, at 80°C and 3500 psi, was similar to that obtained in aqueous medium at 120°C in the presence of dispersing agents.

8‐Substituted 3‐Arylcoumarins as Potent and Selective MAO‐B Inhibitors: Synthesis, Pharmacological Evaluation, and Docking Studies

Neurodegenerative disorders are becoming more prevalent given the increase in the aging population. This has inspired active research in the development of new drugs that could mark an important advance in the treatment of complex diseases such as Alzheimer′s and Parkinson′s. With the aim of finding new MAO‐B‐selective inhibitors, we report the synthesis, in vitro evaluation, and docking simulation of a new series of 3‐arylcoumarins variously substituted at the 8‐position. Most of the studied compounds show high affinity and selectivity for the hMAO‐B isoform, with IC50 values in the low micro‐ to nanomolar range. Some of them have greater hMAO‐B inhibitory activity and selectivity than the reference compound, selegiline. Compounds 7 and 8 are the most active of this series, with compound 8 being fivefold more potent against MAO‐B and severalfold more selective than selegiline. Docking experiments were carried out with hMAO‐B crystal structures, providing new information about the enzyme–inhibitor interaction and the potential therapeutic application of the new 8‐substituted 3‐arylcoumarins.

Hydroxycoumarins as selective MAO-B inhibitors.

A series of 3-aryl-4-hydroxycoumarin derivatives was synthesized with the aim to find out the structural features for the MAO inhibitory activity and selectivity. Methoxy and/or chloro substituents were introduced in the 3-phenyl ring, whereas the position 6 in the coumarin moiety was not substituted or substituted with a methyl group or a chloro atom due to their different electronic, steric and/or lipophilic properties. Most of the synthesized compounds presented MAO-B inhibitory activity. The presence of methoxy and chloro groups, respectively in the para and meta positions of the 3-phenyl ring, have an important influence on the inhibitory activity. Moreover, the presence of a chloro atom in the six position of the moiety (compound 7) improved the inhibitor activity as well as its selectivity against MAO-B compared with iproniazide, used as reference compound. Docking experiments were carried out to understand which are the most energetically preferred orientations adopted by compounds 5, 6 and 7 inside the MAO-B binding pocket.

Monoamine Oxidase Inhibitors: Ten Years of Docking Studies

The number of papers dealing with the structure-based drug design is continuously growing, which demonstrates the importance of such tools in medicinal chemistry. In the current paper, the published literature concerning the use of the ligand-protein docking methodologies in the study of the monoamine oxidase (MAO) enzymes was reviewed. Ten years of studies aimed at developing new compounds active as MAO inhibitors (MAOIs) were covered. The literature regarding thiazole, caffeine, pyrazole, chromone, indeno-pyridazin, β-carboline, indole, coumarin, anilide and amphetamine derivatives, was discussed in some detail. It is apparent that, through this computational approach, more selective and potent molecules can be proposed as inhibitors by applying precise modifications on the basic scaffold.

MAO Inhibitory Activity of 2-Arylbenzofurans versus 3-Arylcoumarins: Synthesis, in vitro Study, and Docking Calculations

Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Several 3‐arylcoumarin derivatives were previously described as interesting selective MAO‐B inhibitors. Preserving the trans‐stilbene structure, a series of 2‐arylbenzofuran and corresponding 3‐arylcoumarin derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO‐A and MAO‐B. In general, both types of derivatives were found to be selective MAO‐B inhibitors, with IC50 values in the nano‐ to micromolar range. 5‐Nitro‐2‐(4‐methoxyphenyl)benzofuran (8) is the most active compound of the benzofuran series, presenting MAO‐B selectivity and reversible inhibition (IC50=140 nM). 3‐(4′‐Methoxyphenyl)‐6‐nitrocoumarin (15), with the same substitution pattern as that of compound 8, was found to be the most active MAO‐B inhibitor of the coumarin series (IC50=3 nM). However, 3‐phenylcoumarin 14 showed activity in the same range (IC50=6 nM), is reversible, and also severalfold more selective than compound 15. Docking experiments for the most active compounds into the MAO‐B and MAO‐A binding pockets highlighted different interactions between the derivative classes (2‐arylbenzofurans and 3‐arylcoumarins), and provided new information about the enzyme–inhibitor interaction and the potential therapeutic application of these scaffolds.

Metallation reactions XXII: Regioselective metallation of (trifluoromethyl)(alkylthio) benzenes

Abstract The metallation reactions of (trifluoromethyl)(alkylthio)benzenes with organolithium reagents and with the butyllithium/potassium tert -butoxide superbasic mixture are here described. The results, according to the theoretical calculations of energy minima, show the monometallation regiochemistry is directed by the sulphur atom. On the other side, the bimetallation, that can be performed only on methylthio derivatives, depends on the organometallic reagent employed. Using butyllithium the stronger coordinative power of sulphur prevails and products metallated in ortho and alpha positions to this atom are mainly formed. With the more basic sec -butyllithium and with the superbase, because of mutual competition between the thioalkyl and trifluoromethyl groups, mixtures of products, coming from metallation in the ortho position to the trifluoromethyl group and in the alpha position of the thiomethylic group, are obtained. In addition, products coming from substitution ortho,alpha to the thiomethyl group are also formed. All mono- and bimetallated intermediates showed to be good synthons for the synthesis of fluoro- and (trifluoromethyl)-substituted benzothiophenes and (trifluoromethyl)benzenes substituted on the thioalkylic chain and/or on the ring.

Addition of 1,3-Benzoxathiole 3-Oxide Anion to Azomethines under Varying Reaction Conditions

The reaction of benzoxathiole 3-oxide with LDA in THF gave an anion which was reacted with azomethines under varying conditions of temperature and solvent. At −78 °C in THF, the two diastereomers resulting from a trans addition were mainly obtained, while at temperatures higher than −40 °C, or upon increasing the solvent polarity, only one trans and one cis diastereomer were obtained. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

METALATION REACTIONS. XXIV. METALATION OF (VINYLTHIO)BENZENE

The addition of organolithium compounds to (vinylthio)benzene (1) and then an electrophilic quenching followed by a further metalation/electrophilic quenching is a general method to prepare in one pot (alkylthio)benzenes ortho,alpha-substituted with equal or different groups. The direct dimetalation of 1 affords the ortho, alpha-dilithiated species 15 besides other by-products. Starting from 15 it is possible to obtain in one step ortho,alpha-substituted (vinylthio)benzenes and heterocyclic compounds.

A re-examination of the methylenation reaction

A re-examination of the methylenation reaction of 1-hydroxy-2-mercapto-, 1,2-dihydroxy- and 1,2-dimercapto-substituted benzenes by bromochloromethane with cesium carbonate shows that these substrates give mixtures of five- and ten-membered benzocondensed heterocyclic compounds and in some cases even dibenzodioxines.