New naphthoquinone derivatives against glioma cells.

This work was aimed to the development of a set of new naphtoquinone derivatives that can act against glioma. The compounds were tested in order to find out their ability to inhibit the growth of glioma cells, and the results of these assays were correlated with electrochemical analysis and NMR-based reoxidation kinetic studies, suggesting that a redox mechanism underlies and may explain the observed biological behavior. In addition to a full description of the synthetic pathways, electrochemistry, NMR and single crystal X-ray diffraction data are provided.

Novel ametantrone-amsacrine related hybrids as topoisomerase IIβ poisons and cytotoxic agents.

The precise definition of the structural requirements for effective topoisomerase II poisoning by drug molecules is still an elusive issue. In the attempt to better define a pharmacophoric pattern, we prepared several conjugates combining the chemical features of two well-known topoisomerase II poisons, amsacrine and ametantrone. Indeed, an appropriate fusion geometry, which entails the anthracenedione moiety of ametantrone appropriately connected to the methanesulfonamidoaniline side chain of amsacrine, elicits DNA-intercalating properties, the capacity to inhibit the human topoisomerase IIβ isoform, and cytotoxic activity resembling that of the parent compounds.

Survival rate in patients affected by dementia followed by memory clinics (UVA) in Italy.

People affected by dementia experienced decreased life expectancy with a 2-4 times higher risk of death at a given age compared to non-demented people. Dementia represents a major cost to health care and society in the Western world and, particularly in Italy, is projected to become a high-resource demanding chronic disease. The present study aimed to estimate the average survival rate of a group of community dwelling elderly affected by dementia in Italy, and to assess the predictive variables associated with survival length.

Ellagic acid and polyhydroxylated urolithins are potent catalytic inhibitors of human topoisomerase II: an in vitro study.

Ellagic acid (EA), a natural polyphenol abundant in fruits and common in our diet, is under intense investigation for its chemopreventive activity resulting from multiple effects. EA inhibits topoisomerase II, but the effects on the human enzyme of urolithins, its monolactone metabolites, are not known. Therefore, the action of several synthetic urolithins toward topoisomerases II was evaluated, showing that polyhydroxylated urolithins, EA, and EA-related compounds are potent inhibitors of the α and β isoforms of human topoisomerase II at submicromolar concentrations.

Urolithin as a converging scaffold linking ellagic acid and coumarin analogues: design of potent protein kinase CK2 inhibitors.

Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (K(i)=20 nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, K(i)=60 nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity.

8-Hydroxynaphthalene-1,4-dione derivative as novel compound for glioma treatment.

Malignant gliomas continue to demand the search for improved chemotherapeutic solutions. In this work the results of a preliminary in vitro screening performed on a small library of compounds are disclosed. As a result 2-(2,4-dihydroxyphenyl)-8-hydroxy-1,4-naphthoquinone emerged as a promising therapeutic lead.

Cyclic carbonate synthesis catalysed by bimetallic aluminium-salen complexes.

The development of bimetallic aluminium-salen complexes [{Al(salen)}(2)O] as catalysts for the synthesis of cyclic carbonates (including the commercially important ethylene and propylene carbonates) from a wide range of terminal epoxides in the presence of tetrabutylammonium bromide as a cocatalyst is reported. The bimetallic structure of one complex was confirmed by X-ray crystallography. The bimetallic complexes displayed exceptionally high catalytic activity and in the presence of tetrabutylammonium bromide could catalyse cyclic carbonate synthesis at atmospheric pressure and room temperature.

Mechanism of cyclic carbonate synthesis from epoxides and CO2.

Three interconnected catalytic cycles account for the title reaction catalyzed by a bimetallic aluminum(salen) complex and Bu(4)NBr. In the first, Bu(4)NBr acts as a nucleophile to activate the epoxide. In the second, Bu(3)N generated in situ serves to activate CO(2).