Antonio Scala

Inhibitory effects of fatty acid monoesters of 2-O-β-d-glucosylglycerol on Epstein–Barr virus activation

In a screening for cancer chemopreventing agents several glycosylglycerols were found to be active. In order to optimize the anti-tumor activity of this class of compounds, a series of 1-O-acyl-2-O-beta-D-glucopyranosyl-sn-glycerols differing in the acyl chain length, which varied from C4 to C18, were examined for their in vitro anti-tumor promoting effects on Epstein-Barr virus early antigen (EBV-BA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the compounds tested, the monohexanoyl derivative was the most active and, noteworthy, the most potent compound of the glycosylglycerol series hitherto known.

1-O-, 2-O- and 3-O-β-glycosyl-sn-glycerols: Structure - anti-tumor-promoting activity relationship

Abstract The inhibitory activity of synthetic glycosylglycerols on Epstein-Barr virus early antigen (EBV-EA) activation was evaluated. Among the series of 1- O -, 2- O - and 3- O - glycosylglycerols tested, 1- O - β -D-galactopyranosyl- sn -glycerol showed the highest inhibitory effect toward promotion.

Anti-tumor-promoting effects of glycoglycerolipid analogues on two-stage mouse skin carcinogenesis.

Four glycoglycerolipid analogues, 1-O-hexanoyl-2-O-beta-D-glucopyranosyl-sn-glycerol (1), 1-O-hexanoyl-2-O-beta-D-galactopyranosyl-sn-glycerol (2), 2-O-(6-O-hexanoyl-beta-D-galactopyranosyl)-sn-glycerol (3) and 2-O-(6-O-hexanoyl-alpha-D-galactopyranosyl)-sn-glycerol (4), potent in vitro inhibitors of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation, were submitted to an in vivo two-stage mouse skin carcinogenesis test, using dimethylbenz[a]anthracene (DMBA) and TPA. The study was extended to two deacylated galactosylglycerol structures, 1-O-beta-D-galactopyranosyl-sn-glycerol (5) and 3-O-beta-D-galactopyranosyl-sn-glycerol (6). All the tested compounds exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion, the 1-hexanoate 2 being the most active among the glycoglycerolipids until now studied.

Regio- and diastereoselective lipase-catalyzed preparation of acetylated 2-O-glucosylglycerols

Abstract 2- O -(β-D-Glucopyranosyl)glycerol and 2- O -(2′,3′,4′,6′-tetra- O -acetyl-β-D-glucopyranosyl]glycerol have been submitted to lipase-catalyzed acetylation using Pseudomonas cepacia (LPS) and Candida antarctica (LCA) Upases in organic solvent. The reactions involved the glycerol moiety and were highly diastereoselective: LPS yielded the (2S)-1- O -acetylderivative, while, more interestingly, LCA yielded the (2R)-1- O -acetyl-derivative; in this way the natural compound lilioside A could be obtained. Conversely, lipase-catalyzed hydrolysis of the fully acetylated 1,3-di- O -acetyl-2- O -(2′,3′,4′,6′-tetra- O -acetyl-β-D-glucopyranosyl)glycerol using LCA fiunished the (2S)-1- O -acetyl-derivative showing the same steric preference as the reverse reaction.

Epimerization of α- to β-C-glucopyranosides under mild basic conditions

A number of β-C-glucopyranosides having an activated methylene or methine group bonded to the anomeric carbon are obtainable in quantitative yield from the corresponding α-isomers by simple equilibration catalysed by various bases at room temperature.

Inhibitory effects of monoacylated 2-O-β-galactosylglycerols on Epstein-Barr virus activation : the significant role of the hexanoyl chain

Three series of monoacyl-2-O-beta-D-galactosylglycerols bearing an acyl chain of varying length, from C4 to C10, were studied due to their antitumor promoting effects on the activation of the Epstein-Barr virus early antigen (EBV-EA), such activation being induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study indicates that it is more the length of the acyl chain that is important for the activity, six carbon atoms resulting in maximum effect, rather than the position of the ester function and the nature of the sugar (galactose or glucose).

Glycoglycerolipid analogues active as anti-tumor-promoters: the influence of the anomeric configuration.

The in vitro anti-tumor promoting effect of monohexanoates of 2-O-alpha-D-gluco- and galactopyranosyl-sn-glycerol on the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation was evaluated and compared to the potencies of the corresponding beta-anomers. The results show that the inversion of the anomeric configuration from beta to alpha does not seem to significantly influence the activity, which is present, as for the beta-anomers, even at 1x10 mol ratio without any cytotoxicity.

Hydrogen Exchange and Double Bond Formation in Cholesterol Biosynthesis

The conversion of lanosterol║to cholesterol requires a considerable number of intermediary steps involving loss or uptake of hydrogen atoms and formation and migration of nuclear double bonds. Detailed discussions on the intermediary steps in cholesterol biosynthesis are reported in several reviews (Olson 1965; Frantz & Schroepfer 1967; Goad 1970). In the present report some mechanisms in the formation of cholesterol and its sterol precursors from lanosterol are discussed. The relation between in vitro and in vivo pathways of cholesterol biosynthesis and the composition and metabolism of sterols in biological tissues is underlined.

Bioactive glycoglycerolipid analogues: an expeditious enzymatic approach to mono- and diesters of 2-O-β-d-galactosylglycerol

Abstract 2-O-β- d -Galactosylglycerol 1 was submitted to acylation using Pseudomonas cepacia or Candida antarctica lipases as catalysts and 2,2,2-trifluoroethyl esters of butanoic, hexanoic, octanoic or decanoic acid as acyl carriers. Taking advantage of the high diastereoselectivity and regioselectivity of the two enzymes, the 1-O-, 3-O-, 6′-O-acyl and the 1,6′-di-O-acylderivatives of 1 were obtained pure or in an appreciably enriched form.

Optically pure 1-O- and 3-O-β-D-glucosyl- and galactosyl-sn-glycerols through lipase-catalyzed transformations

Abstract Pseudomonas cepacia lipase shows opposite stereoselectivity in the acylation versus the deacylation of diastereoisomeric 1- O - and 3- O - β -D-glycopyranosyl- sn -glycerols: while the 2,3,4,6-tetraacetylated 1- O -glycosyl- sn -glycerols were the preferred substrates in the former reaction, the 3- O -peracetylated derivatives were hydrolyzed in the latter one. In this way, both 1- O - and 3- O -stereoisomers could be obtained optically pure as residual substrates.