Damiano Tanini

Evaluation of selenide, diselenide and selenoheterocycle derivatives as carbonic anhydrase I, II, IV, VII and IX inhibitors

A series of selenides, diselenides and organoselenoheterocycles were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, IV, VII and IX, involved in a variety of diseases among which glaucoma, retinitis pigmentosa, epilepsy, arthritis and tumors etc. These investigated compounds showed inhibitory action against these isoforms and some of them were selective for inhibiting the cytosolic over the membrane-bound isoforms, thus making them interesting leads for the development of isoform-selective inhibitors.

Novel sulfur and selenium-containing antioxidants: Synthesis and evaluation of their GPx-like activity

GRAPHICAL ABSTRACT ABSTRACT New linear and cyclic chalcogen-containing compounds have been synthesized exploiting the reactivity of bis(trimethylsilyl)selenide with strained heterocycles. A simple and efficient procedure allowed a selective access to β-functionalized selenides, diselenides, and dithiaselenepanes under mild conditions. Antioxidant catalytic activity of these compounds was investigated in the reaction of hydrogen peroxide with dithiothreitol (DTTred). According to this assay, some of the synthesized structures exhibited a remarkable glutathione peroxidase (GPx)-like activity.

Thiosilane- and Organoselenosilane-Mediated Novel Access to 3,7-Disubstituted-1,2,5- trithiepanes and -1,2,5-dithiaselenepanes

The reaction of bis(trimethylsilyl) sulfide with different substituted thiiranes under tetrabutylammonium fluoride (TBAF) catalysis leads to the synthesis of 3,7-disubstituted-1,2,5-trithiepanes, through regioselective reaction of a thiosilane intermediate with another molecule of episulfide, followed by intramolecular oxidation of two sulfur units. When using bis(trimethylsilyl)selenide, the reaction with thiiranes and TBAF affords a smooth access to a novel class of disubstituted-1,2,5-dithiaselenepanes.

Discovery of New Selenoureido Analogues of 4-(4-Fluorophenylureido)benzenesulfonamide as Carbonic Anhydrase Inhibitors

A series of benzenesulfonamides bearing selenourea moieties was obtained considering the ureido-sulfonamide SLC-0111, in Phase I clinical trials as antitumor agent, as a lead molecule. All compounds showed interesting inhibition potencies against the physiologically relevant human (h) carbonic anhydrase (hCAs, EC 4.2.1.1) isoforms I, II, IV, and IX. The most flexible analogues in the series 14-19 showed low nanomolar inhibition constants against hCA I, II, and IX. We assessed selected compounds on the in vitro antioxidant properties and binding modes and evaluated ex vivo human prostate (PC3), breast (MDA-MB-231), and colon-rectal (HT-29) cancer cell lines both in normoxic and hypoxic conditions.

First evaluation of organotellurium derivatives as carbonic anhydrase I, II, IV, VII and IX inhibitors

A series of tellurides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) carbonic anhydrase isoforms hCA I, II, IV, VII and IX, involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis and tumors. These compounds, which are the first tellurium-containing derivatives acting as inhibitors of carbonic anhydrase enzymes, showed effective inhibition against all isoforms investigated and some of them were selective for inhibiting the cytosolic or the membrane-bound CAs. Thus, these carbonic anhydrase inhibitors are interesting leads for the development of isoform-selective inhibitors.

Silicon-Assisted Synthesis and Functionalization of Sulfurated and Selenated Compounds

GRAPHICAL ABSTRACT Abstract The synthetic potential of thiosilanes and selenosilanes toward various electrophiles is described, focusing on the synthesis of a representative range of thiocarbonyl, selenocarbonyl, β-functionalized compounds, and acyl-seleno derivatives. Reactions of silyl chalcogenides with epoxides, episulfides, and aziridines allowed the synthesis of β-hydroxy, β-mercapto, and β-amino thiols, as well as of β-substituted selenides and diselenides. A peculiar behavior was observed in the reaction with episulfides, leading to seven-membered trithia- and dithiaseleno-heterocycles. Furthermore, carbodesilylation of α-heterosubstituted organosilanes provided a smooth access to benzothiophene and benzofuran-derivatives.

Synthesis of Novel Selenides Bearing Benzenesulfonamide Moieties as Carbonic Anhydrase I, II, IV, VII, and IX Inhibitors

A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for the inhibition of five human (h) isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA I, II, IV, VII, and IX. These enzymes are involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis, and tumors. The investigated compounds showed potent inhibitory action against hCA II, VII, and IX, in the low nanomolar range, thus making them of interest for the development of isoform-selective inhibitors and as candidates for biomedical applications.

Aziridines Ring Opening by Silyl Chalcogenides: a Stereoselective Access to Polyfunctionalized Molecules as Precursor of Sulfurated and Selenated Heterocycles

GRAPHICAL ABSTRACT Abstract Aziridines react efficiently with bis(trimethyl)silyl-sulfide and -selenide to afford a direct access to β-amino thiols and selenols. Synthesis of 2,4-disubstituted 1,3-selenazolidines is obtained through reaction of 1,2-amino selenols with aldehydes.

Synthesis of A New Class of Sulfurated and Selenated Silyl Heterocycles

Abstract 2-Trimethylsilyl-1,3-thiaselenolanes and 2-trimethylsilyl-1,3-oxaselenolanes can be accessed through the reaction of a silyl acetal with β-mercapto- and β-hydroxyselenols under Lewis acid conditions. GRAPHICAL ABSTRACT

Selective access to sulfurated and selenated heterocycles by intramolecular cyclization of β-substituted sulfides and selenides

GRAPHICAL ABSTRACT ABSTRACT δ-Hydroxy- and δ-amino α-thio-esters, easily obtainable through S-alkylation of β-mercapto alcohols and β-amino thiols with bromo acetate, behave as suitable starting compounds to obtain various 2-hydroxy-1,4-oxathianes and (S)-3,4-dihydro-2H-1,4-thiazines via a reductive ring closure. Under similar conditions, selenated heterocycles are also synthesized.