- Design, physico-chemical characterization andin vitrobiological activity of organogold(iii) glycoconjugates
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To develop new metal-based glycoconjugates as potential anticancer agents, four organometallic gold(iii)-dithiocarbamato glycoconjugates of the type [AuIII(2-Bnpy)(SSC-Inp-GlcN)](PF6) (2-Bnpy: 2-benzylpyridine; Inp: isonipecotic moie
- Pettenuzzo, Andrea,Vezzù, Keti,Di Paolo, Maria Luisa,Fotopoulou, Eirini,Marchiò, Luciano,Via, Lisa Dalla,Ronconi, Luca
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supporting information
p. 8963 - 8979
(2021/07/02)
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- The strategic use of: Para-quinone methides to access synthetically challenging and chemoselective α,α-diarylmethyl N-glycosides from unprotected carbohydrate amines
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Reported herein is a practical route to access synthetically challenging and chemoselective α,α-diarylmethyl N-glycosides via Sc(OTf)3-catalyzed 1,6-conjugate addition of amino sugars with para-quinone methides (p-QMs). The reactions proceed smoothly without a base and under mild reaction conditions with a broad substrate scope and moderate to good yields.
- Sangwan, Rekha,Dubey, Atul,Tiwari, Ashwani,Mandal, Pintu Kumar
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supporting information
p. 1343 - 1348
(2020/03/03)
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- An innovative and efficient route to the synthesis of metal-based glycoconjugates: proof-of-concept and potential applications
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With a view to developing more efficient strategies to the functionalization of metallodrugs with carbohydrates, we here report on an innovative and efficient synthetic route to generate gold(iii) glycoconjugates in high yields and purity. The method is based on the initial synthesis of the zinc(ii)-dithiocarbamato intermediate [ZnII(SSC-Inp-GlcN)2] (Inp = isonipecotic moiety; GlcN = amino-glucose) followed by the transfer of the glucoseisonipecoticdithiocarbamato ligand to the gold(iii) center via transmetallation reaction between the zinc(ii) intermediate and K[AuIIIBr4] in 1?:?2 stoichiometric ratio, yielding the corresponding glucose-functionalized gold(iii)-dithiocarbamato derivative [AuIIIBr2(SSC-Inp-GlcN)]. No protection/deprotection of the amino-glucose scaffold and no chromatographic purification were needed. The synthetic protocol was optimized for glucose precursors bearing the amino function at either the C2 or the C6 position, and works in the case of both α and β anomers. The application of the synthetic strategy was also successfully extended to other metal ions of biomedical interest, such as gold(i) and platinum(ii), to obtain [AuI(SSC-Inp-GlcN)(PPh3)] and [PtII(SSC-Inp-GlcN)2], respectively. All compounds were fully characterized by elemental analysis, mid- and far-IR, mono- and multidimensional NMR spectroscopy, and, where possible, X-ray crystallography. Results and potential applications are here discussed.
- Pettenuzzo, Andrea,Montagner, Diego,McArdle, Patrick,Ronconi, Luca
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supporting information
p. 10721 - 10736
(2018/08/17)
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- Cinnamide Derivatives of d-Mannose as Inhibitors of the Bacterial Virulence Factor LecB from Pseudomonas aeruginosa
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Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen with high antibiotic resistance. Its lectin LecB was identified as a virulence factor and is relevant in bacterial adhesion and biofilm formation. Inhibition of LecB with carbohydrate-based ligands results in a decrease in toxicity and biofilm formation. We recently discovered two classes of potent drug-like glycomimetic inhibitors, that is, sulfonamides and cinnamides of d-mannose. Here, we describe the chemical synthesis and biochemical evaluation of more than 20 derivatives with increased potency compared to the unsubstituted cinnamide. The structure–activity relationship (SAR) obtained and the extended biophysical characterization allowed the experimental determination of the binding mode of these cinnamides with LecB. The established surface binding mode now allows future rational structure-based drug design. Importantly, all glycomimetics tested showed extended receptor residence times with half-lives in the 5–20 min range, a prerequisite for therapeutic application. Thus, the glycomimetics described here provide an excellent basis for future development of anti-infectives against this multidrug-resistant pathogen.
- Sommer, Roman,Hauck, Dirk,Varrot, Annabelle,Wagner, Stefanie,Audfray, Aymeric,Prestel, Andreas,M?ller, Heiko M.,Imberty, Anne,Titz, Alexander
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p. 756 - 767
(2016/07/06)
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- Cinnamide Derivatives of d-Mannose as Inhibitors of the Bacterial Virulence Factor LecB from Pseudomonas aeruginosa
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Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen with high antibiotic resistance. Its lectin LecB was identified as a virulence factor and is relevant in bacterial adhesion and biofilm formation. Inhibition of LecB with carbohydrate-based ligands results in a decrease in toxicity and biofilm formation. We recently discovered two classes of potent drug-like glycomimetic inhibitors, that is, sulfonamides and cinnamides of d-mannose. Here, we describe the chemical synthesis and biochemical evaluation of more than 20 derivatives with increased potency compared to the unsubstituted cinnamide. The structure–activity relationship (SAR) obtained and the extended biophysical characterization allowed the experimental determination of the binding mode of these cinnamides with LecB. The established surface binding mode now allows future rational structure-based drug design. Importantly, all glycomimetics tested showed extended receptor residence times with half-lives in the 5–20 min range, a prerequisite for therapeutic application. Thus, the glycomimetics described here provide an excellent basis for future development of anti-infectives against this multidrug-resistant pathogen.
- Sommer, Roman,Hauck, Dirk,Varrot, Annabelle,Wagner, Stefanie,Audfray, Aymeric,Prestel, Andreas,M?ller, Heiko M.,Imberty, Anne,Titz, Alexander
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p. 756 - 767
(2016/08/28)
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- Synthesis and glycosidase inhibitory profiles of functionalised morpholines and oxazepanes
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In this work libraries of morpholines and oxazepanes have been prepared via the reductive amination reaction between dialdehydes, derived from carbohydrates, and a range of amines. In this way, functionalised morpholines and oxazepanes have been prepared
- Burland, Peter A.,Osborn, Helen M.I.,Turkson, Andrea
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experimental part
p. 5679 - 5692
(2011/10/31)
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- Quantifying the electronic effects of carbohydrate hydroxy groups by using aminosugar models
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Methyl amino-deoxy-glycosides with α- and β-gluco, α-galacto, or α-manno stereochemistry with the amino functionality in each of the four possible non-anomeric positions have been synthesized and their pKa values determined by titration. These
- Pedersen, Christian M.,Olsen, Jacob,Brka, Azra B.,Bols, Mikael
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supporting information; experimental part
p. 7080 - 7086
(2011/07/08)
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- Synthesis and α-Glucosidase II inhibitory activity of valienamine pseudodisaccharides relevant to N-glycan biosynthesis
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Valienol-derived allylic C-1 bromides have been used as carbaglycosyl donors for α-xylo configured valienamine pseudodisaccharide synthesis. We synthesised valienamine analogues of the Glc(α1→3)Glc and Glc(α1→3)Man disaccharides representing the linkages
- Cumpstey, Ian,Ramstadius, Clinton,Eszter Borbas,Alonzi, Dominic S.,Butters, Terry D.
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supporting information; experimental part
p. 5219 - 5223
(2011/10/09)
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- Synthesis and antibacterial activity of aminodeoxyglucose derivatives against Listeria innocua and Salmonella typhimurium
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In this study aminodeoxyglucose derivatives were synthesized and evaluated for their antibacterial activity against two food bacteria, Listeria innocua and Salmonella typhimurium. 6-Amino-6-deoxy-α-Dmethylglucopyranose (GSA-6), 3-amino-3-deoxy-D-glucopyranoside (GSA-3), and β-D-glucopyranosylamine (GSA-1) were synthesized and concurrently tested with commercially available D-glucosamine (GSA-2) for antibacterial activity. Results obtained from this study showed a pronounced antagonist effect due to the position of amino groups of aminoglucose derivatives on the antibacterial activity. GSA-3 was the most active compound. At a concentration of 2 × 10 -4 mol mL -1, it delayed the growth of both bacteria with percentages of inhibition of 29 and 15% for L. innocua and S. typhimurium, respectively. At the same concentration the percentages of inhibition for other aminodeoxyglucoses varied between 5 and 18% and between 2 and 11% for L. innocua and S. typhimurium, respectively. All compounds were characterized by FTIR, 1H NMR, and 13C NMR spectroscopy.
- Theoneste, Muhizi,Stephane, Greller,Veronique, Coma
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experimental part
p. 8770 - 8775
(2010/07/17)
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- METHODS, COMPOUNDS, COMPOSITIONS AND VEHICLES FOR DELIVERING 3-AMINO-1-PROPANESULFONIC ACID
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The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compounds that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to, the prevention and treatment of Alzheimer's disease.
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Page/Page column 49-50
(2008/12/06)
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- Constituents of Ocimum sanctum with antistress activity
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Three new compounds, ocimumosides A (1) and B (2) and ocimarin (3), were isolated from an extract of the leaves of holy basil (Ocimum sanctum), together with eight known substances, apigenin, apigenin-7-O-β-D-glucopyranoside, apigenin-7-O-β-D-glucuronic acid (4), apigenin-7-O-β-D-glucuronic acid 6″-methyl ester, luteolin-7-O-β-D-glucuronic acid 6″-methyl ester, luteolin-7-O-β-D-glucopyranoside, luteolin-5-O-β-D- glucopyranoside, and 4-allyl-1-O-β-D-glucopyronosyl-2-hydroxybenzene (5), and two known cerebrosides. The structures of the new compounds were determined on the basis of extensive 1D and 2D NMR spectroscopic analysis. The new compounds (1-3) and the known compounds 4 and 5 were screened at a dose of 40 mg/kg body weight for acute stress-induced biochemical changes in male Sprague-Dawley rats. Compound 1 displayed promising antistress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 2 and 5 were also effective in normalizing most of these stress parameters. In contrast, compounds 3 and 4 were ineffective in normalizing any of these effects.
- Gupta, Prasoon,Yadav, Dinesh Kumar,Siripurapu, Kiran Babu,Palit, Guatam,Maurya, Rakesh
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p. 1410 - 1416
(2008/04/01)
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- Avrainvilloside, a 6-deoxy-6-aminoglucoglycerolipid from the green alga Avrainvillea nigricans
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Fractionation of the organic extract obtained from the Dominican green alga Avrainvillea nigricans led to the isolation of avrainvilloside (2), a new glycoglycerolipid bearing the extremely rare 6-deoxy-6-aminoglucose moiety. The structure of avrainvilloside has been established on the basis of spectroscopic data and methanolysis/GC-MS analysis.
- Andersen, Raymond J.,Taglialatela-Scafati, Orazio
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p. 1428 - 1430
(2008/09/19)
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- New glycoconjugated cyanine dyes as fluorescent labeling reagents
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New highly water soluble cyanine dyes incorporating methyl glucopyranoside residues and reactive functionality are synthesised. The new dyes are conjugated to aminodextrans and to antibodies. The absorption and fluorescence properties of the new dyes and of the labeled substrates are discussed.
- Reddington, Mark V.
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p. 143 - 147
(2007/10/03)
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- Chiral 2-Thioxotetrahydro-1,3-O,N-heterocycles from Carbohydrates. 2. Stereocontrolled Synthesis of Oxazolidine Pseudo-C-nucleosides and Bicyclic Oxazine-2-thiones
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Chiral, sugar-derived oxazolidine-2-thiones having a pseudo-C-nucleoside structure, as well as bicyclic 2-thioxotetrahydro-1,3-oxazines, have been prepared by intramolecular cyclization of 6-deoxy-6-isothiocyanatoaldoses or -aldopyranosides, respectively.The reaction proceeds with total regioselectivity and no need for protection of the secondary hydroxyl groups.A one-pot procedure for the synthesis of the five-membered heterocycles from the corresponding amino sugars is aslo reported.The six-membered analogs have a cis- or trans-decalin-type core depending on the configuration of the sugar precursor.
- Fernandez, Jose M. Garcia,Mellet, Carmen Ortiz,Fuentes, Jose
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p. 5192 - 5199
(2007/10/02)
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