Adele Bolognese

Synthesis and structure-activity relationships of 2-(substituted phenyl)-3-[3-(N, N-dimethylamino)propyl]-1,3-thiazolidin-4-ones acting as H1-histamine antagonists

2-(Substituted-phenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidi n-4- ones (1-15) showed dependence of the potency of the H1-histamine antagonism on the m- and p-substituents suggesting that the aromatic moiety binds the receptor by a strong pi-interaction. Electron-withdrawing substituents decrease the potency while the electron-donating alkyl substituents, enhancing the aryl HOMO energy, increase the antihistamine activity. The m-substituents with the capability to form hydrogen bonds, seems to share an extra-interaction with hydrogen accepting or donating groups of the histamine receptor and exhibits very high potency.

Nutraceutical properties and polyphenolic profile of berry skin and wine of Vitis vinifera L. (cv. Aglianico)

Red grapes are rich in phenolics, flavonoids, anthocyanins and resveratrol, all substances which have been suggested as having nutraceutical and health benefits. The berry skin and wine of grape cultivar Vitis vinifera L. (cv. Aglianico), grown in Basilicata (Southern Italy) were examined to determinate the presence of the above mentioned compounds as well as to establish the inorganic cation profile. HPLC analysis coupled with LC-ESI/MS/MS detected high contents of total flavonols and anthocyanins in berry skin and wine. The wine made with the same grape used for berry skin assays showed a notable presence of quercetin-3-O-glucoside (39.4% of total flavonols), and malvidin and petunidin derivatives (63.9% and 10.8% of total anthocyanins, respectively). The strong antioxidant ROS-scavenging activity, determined by both DPPH and FRAP assays, and the high resveratrol content confer high sensory characteristics resulted to be associated with positive nutraceutical properties of these grapes and wine. The level of cis-resveratrol was lower than trans-resveratrol in both berry skin and wine reaching 44.1mg/kg and 0.3mg/l, respectively. The cation profile presents low levels of Ca, Cu, K, Fe, Zn and Cd compared to numerous, important red wines, such as Monastrell and Tempranillo.

Thiazolidin-4-one formation. Mechanistic and synthetic aspects of the reaction of imines and mercaptoacetic acid under microwave and conventional heating

Microwave irradiation of a mixture of benzylidene-anilines and mercaptoacetic acid in benzene gives 1,3-thiazolidin-4-ones in very high yield (65-90%), whereas the same reaction performed through using the conventional method, at reflux temperature, requires a much longer time and gives a much lower yield (25-69%). This difference seems to be due to some intermediates and by-products formed during the conventional reaction. On the basis of 1H NMR studies, two different mechanisms, acting in benzene and in DMF, respectively, have been hypothesized for the thiazolidin-4-one system formation.

New benzo[g]isoquinoline-5,10-diones and dihydrothieno [2,3-b]naphtho-4,9-dione derivatives: synthesis and biological evaluation as potential antitumoral agents.

Novel antitumoral agents with quinonic structure were synthesized and evaluated for their in vitro cytotoxic activities. This study examines the cytotoxic activities of several aryl benzo[g]isoquinoline-5,10-dione derivatives and a number of aminoacyl dihydrothieno[2,3-b]naphtho-4,9-dione (DTNQ) derivatives containing amino acids in position 3 of the ring system. Compound 6 showed remarkable cytotoxic activity at submicromolar concentration not only against several human leukaemia and solid tumour cell lines, but also toward sensitive and resistant human cell lines.

Mechanochemistry of ibuprofen pharmaceutical.

In this paper mechanochemistry has been studied in view of possible application to detoxification of expired pharmaceuticals. The experiments have been carried out with a commercial medication containing ibuprofen ((RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid) which has been submitted to prolonged milling up to 40h. When Al(OH)(3) is used as co-reagent, the first degradation step induced by the mechanochemical treatment is an acid-base reaction with the ibuprofen carboxylic acid group. The subsequent degradation follows a complex pathway leading to 1-(4-isobutylphenyl)ethanone, 1-isobutyl-4-vinylbenzene and 2-(4-(3-methylbutan-2-yl)phenyl)propan-1-ol after 10h milling and, in addition, 1-(4-acetylphenyl)-2-methylpropan-1-one, 1-(4-(1-hydroxy-2-methylpropyl)phenyl)ethanone and 1-(4-(2-hydroxy-2-methylpropyl)phenyl)ethanone after 40h milling. The degradation reaction path and products have been identified by means of FT-IR spectroscopy, thin layer chromatography, NMR spectroscopy, mass spectroscopy and elemental analysis. The observed ibuprofen decarboxylation makes the drug simultaneously lose both its pharmaceutical activity and toxicity.

On the azetidin-2-one ring formation. A 1H NMR investigation

Abstract Azetidin-2-ones were prepared by addition of phenylacetic acid chloride to substituted benzal-anilines in DMF. The effect of temperature and substituents at the benzal-anilines on the reaction mechanism was investigated carrying out the reaction in DMF d7 in an NMR probe of a Bruker 400-MHz spectrometer at 25 and 60 °C. Proton signals, arising from two kinds of intermediates a 2-phenyl-N-(α-chlorobenzyl)-acetanilide (6) and a nitrogen-charged adduct (7) suggest that two competitive mechanisms play a role in the formation of trans and cis azetidin-2-ones. The Staudinger reaction mechanism was investigated by NMR experiments.

An NMR Study of the Bortezomib Degradation under Clinical Use Conditions.

The (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl-boronic acid, bortezomib (BTZ), which binds the 20S proteasome subunit and causes a large inhibition of its activity, is a peptidomimetic boronic drug mainly used for the treatment of multiple myeloma. Commercial BTZ, stabilized as mannitol derivative, has been investigated under the common conditions of the clinical use because it is suspected to be easily degradable in the region of its boronic moiety. Commercial BTZ samples, reconstituted according to the reported commercial instructions and stored at 4°C, were analyzed by high-field nuclear magnetic resonance spectroscopy in comparison with identical samples bubbled with air and argon, respectively. All the samples remained unchanged for a week. After a month, the air filled samples showed the presence of two main degradation products (6% of starting material), the N-(1-(1-hydroxy-3-methylbutylamino)-1-oxo-3-phenylpropan-2-yl) pyrazine-2-carboxamide (BTZ1; 5%, determined from NMR integration) and the (S)-N-(1-(3-methylbutanamido)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxamide (BTZ2; 1%, determined from NMR integration), identified on the basis of their chemical and spectroscopic properties. The BTZ1 and BTZ2 finding suggests that, under the common condition of use and at 4°C, commercial BTZ-mannitol is stable for a week, and that, in time, it undergoes slow oxidative deboronation which partially inactivates the product. Low temperature and scarce contact with air decrease the degradation process.

Antidiarrhoeal activity of new thiazolidinones related to loperamide.

A series of thiazolidinones related to loperamide was synthesized and evaluated for antidiarrhoeal activity in mice, using the castor oil test.

Quantitative structure-activity relationships in a set of thiazolidin-4-ones acting as H1-histamine antagonists

A series of 2-(3- and 4-substituted phenyl)-3-[3-(N, N-dimethyl-amino)propyl]-1,3-thiazolidin-4-ones acting as H1-antihistaminics was investigated with a combined Hansch-CoMFA approach. The substituents at the 3- and 4-positions of the phenyl ring have been described through steric, electronic and hydrophobic parameters and correlated with pA2 values. The obtained quantitative models suggest that affinity to the receptor is promoted by hydrophobic and small 4-substituents and by 3- and 4-substituents generating a positive electrostatic potential towards a complementary receptor region.

Anthocyanin composition and extractability in berry skin and wine of Vitis vinifera L. cv. Aglianico

BACKGROUND The present article reports the anthocyanin content in the berry skin and wine of the Italian red grape cultivar Aglianico (clone VCR11 grafted onto 1103 Paulsen), one of the most ancient vines and famous for its deep-red colour. Anthocyanins were extracted from frozen berry skin in an acidified methanol solution. The extraction mixtures, monitored for 120 h, were analysed by high-performance liquid chromatography. RESULTS The extraction from berry skin of delphinidin, petunidin and malvidin appeared to be a time-independent process, whereas the concentration of peonidin increased linearly with time. Peonidin-O-acetyl-glucoside was transferred from skin more slowly than petunidin-O-acetyl-glucoside and malvidin-O-acetyl-glucoside. The anthocyanin composition of the resulting wine showed that the total anthocyanin content was about one-tenth of the corresponding berry skin content. The ratio acetyl/coumaroyl anthocyanins in the wine was sharply higher than the value in berry skin (0.85 and 0.10, respectively), indicating an enrichment of acetyl derivatives in the wine. CONCLUSION Levels of single anthocyanins in wine were not always correlated with those detected in grapes, as they were affected by winemaking. The high values of some anthocyanins in Aglianico wine could ameliorate its quality, increasing the chromatic properties, aging stability and product acceptance.