The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Yoel Kashman - One of the best experts on this subject based on the ideXlab platform.
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Salarins A and B and Tulearin A: New Cytotoxic Sponge-Derived Macrolides
Organic Letters, 2008Co-Authors: Ashgan Bishara, Amira Rudi, Maurice Aknin, Drorit Neumann, Nathalie Ben-califa, Yoel KashmanAbstract:Three novel nitrogenous macrolides designated salarin A (e.g. I) and B (II) and tulearin A were isolated from the Madagascar Fascaplysinopsis sp. sponge. The structures of the compds. were elucidated by interpretation of MS and 1D and 2D NMR spectra. Both salarins carry an acetylCarbamate moiety, and in addn., I contains a triacylamine group and II a methoxymethylketone lactam. Tulearin A carries the naturally rare Carbamate Ester. The compds. were found to be toxic to brine shrimp larvae, and salarin A and tulearin A were also cytotoxic to leukemia cells. [on SciFinder(R)]
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Salarins a and B and tulearin a: new cytotoxic sponge-derived macrolides.
Organic letters, 2007Co-Authors: Ashgan Bishara, Amira Rudi, Maurice Aknin, Drorit Neumann, Nathalie Ben-califa, Yoel KashmanAbstract:Three novel nitrogenous macrolides designated salarin A and B (1 and 2) and tulearin A (3) were isolated from the Madagascar Fascaplysinopsis sp. sponge. The structures of the compounds were elucidated by interpretation of MS and 1D and 2D NMR spectra. Both salarins carry an acetylCarbamate moiety, and in addition, 1 contains a triacylamine group and 2 a methoxymethylketone lactam. Tulearin A carries the naturally rare Carbamate Ester. The compounds were found to be toxic to brine shrimp larvae, and salarin A and tulearin A were also cytotoxic to leukemia cells.
V.i. Kovalenko - One of the best experts on this subject based on the ideXlab platform.
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DFT study of structure, IR and Raman spectra of the first generation dendron built from cyclotriphosphazene core with terminal Carbamate and Ester groups
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2012Co-Authors: V.l. Furer, A.e. Vandyukov, S. Fuchs, J.p. Majoral, A.m. Caminade, V.i. KovalenkoAbstract:The FTIR and FT-Raman spectra of the first generation dendron built from the cyclotriphosphazene core, five arms OC6H4CHNN(CH3)P(S) with ten Carbamate terminal groups and one Ester function Gv1 have been recorded. The IR and Raman spectra of the zero generation dendron Gv0 and first generation dendrimer G1 with the same core and terminal groups were also examined. The structural optimization and normal mode analysis were performed for dendron Gv1 on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that Gv1 has a concave lens structure with planar OC6H4CHNN(CH3)P(S) fragments and slightly non-planar cyclotriphosphazene core. The Carbamate groups attached to different arms show significant deviations from a symmetrical arrangement relative to the local planes of repeating units. The experimental IR spectrum of Gv1 dendron was interpreted by means of potential energy distributions. The strong band 1604 cm−1 shows marked changes of the optical density in dependence of the Carbamate, Ester or azomethyne substituents in the aromatic ring. The frequencies of ν(NH) and ν(CO) bands in the IR spectra reveal the presence of the different types of H-bonds in the studied dendrimers
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DFT study of structure, IR and Raman spectra of the first generation dendron built from cyclotriphosphazene core with terminal Carbamate and Ester groups.
Spectrochimica acta. Part A Molecular and biomolecular spectroscopy, 2012Co-Authors: V.l. Furer, A.e. Vandyukov, S. Fuchs, J.p. Majoral, A.m. Caminade, V.i. KovalenkoAbstract:The FTIR and FT-Raman spectra of the first generation dendron built from the cyclotriphosphazene core, five arms -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds on the righthand side with ten Carbamate terminal groups and one Ester function G(v1) have been recorded. The IR and Raman spectra of the zero generation dendron G(v0) and first generation dendrimer G(1) with the same core and terminal groups were also examined. The structural optimization and normal mode analysis were performed for dendron G(v1) on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that G(v1) has a concave lens structure with planar -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds on the righhand side fragments and slightly non-planar cyclotriphosphazene core. The Carbamate groups attached to different arms show significant deviations from a symmetrical arrangement relative to the local planes of repeating units. The experimental IR spectrum of G(v1) dendron was interpreted by means of potential energy distributions. The strong band 1604 cm(-1) shows marked changes of the optical density in dependence of the Carbamate, Ester or azomethyne substituents in the aromatic ring. The frequencies of ν(N-H) and ν(C=O) bands in the IR spectra reveal the presence of the different types of H-bonds in the studied dendrimers.
Lucia Biasutto - One of the best experts on this subject based on the ideXlab platform.
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Amino Acid Carbamates As Prodrugs Of Resveratrol
Scientific Reports, 2015Co-Authors: Andrea Mattarei, Michele Azzolini, Cristina Paradisi, Mario Zoratti, Martina La Spina, Lucia BiasuttoAbstract:Resveratrol (3, 5, 4′-trihydroxy- trans -stilbene), a plant polyphenol, has important drug-like properties, but its pharmacological exploitation in vivo is hindered by its rapid transformation via phase II conjugative metabolism. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, stability and in vivo pharmacokinetic behaviour of prodrugs of resveratrol in which the OH groups are engaged in an N-monosubstituted Carbamate Ester (-OC(O)NHR) linkage with a natural amino acid (Leu, Ile, Phe, Thr) to prevent conjugation and modulate the physicochemical properties of the molecule. We also report a convenient, high-yield protocol to obtain derivatives of this type. The new Carbamate Ester derivatives are stable at pH 1, while they undergo slow hydrolysis at physiological pH and hydrolyse with kinetics suitable for use in prodrugs in whole blood. After administration to rats by oral gavage the isoleucine-containing prodrug was significantly absorbed and was present in the bloodstream as non-metabolized unaltered or partially deprotected species, demonstrating effective shielding from first-pass metabolism. We conclude that prodrugs based on the N-monosubstituted Carbamate Ester bond have the appropriate stability profile for the systemic delivery of phenolic compounds.
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N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol.
Molecules (Basel Switzerland), 2015Co-Authors: Andrea Mattarei, Michele Azzolini, Mario Zoratti, Lucia Biasutto, Cristina ParadisiAbstract:Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted Carbamate Ester linkage. As promoiety, methoxy-oligo(ethylene glycol) groups (m-OEG) (CH₃-[OCH₂CH₂]n-) of defined chain length (n = 3, 4, 6) were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol) (PEG) chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption.
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Synthesis and Evaluation as Prodrugs of Hydrophilic Carbamate Ester Analogues of Resveratrol.
Molecular pharmaceutics, 2015Co-Authors: Michele Azzolini, Andrea Mattarei, Cristina Paradisi, Mario Zoratti, Martina La Spina, Ester Marotta, Lucia BiasuttoAbstract:Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is an unfulfilled promise for health care: its exploitation is hindered by rapid conjugative metabolism in enterocytes and hepatocytes; low water solubility is a serious practical problem. To advantageously modify the physicochemical properties of the compound we have developed prodrugs in which all or part of the hydroxyl groups are linked via an N-monosubstituted Carbamate Ester bond to promoieties derived from glycerol or galactose, conferring higher water solubility. Kinetic studies of hydrolysis in aqueous solutions and in blood indicated that regeneration of resveratrol takes place in an appropriate time frame for delivery via oral administration. Despite their hydrophilicity some of the synthesized compounds were absorbed in the gastrointestinal tract of rats. In these cases the species found in blood after administration of a bolus consisted mainly of partially deprotected resveratrol derivatives and of the products of their glucuronidation, thus providing proof-of-principle evidence of behavior as prodrugs. The soluble compounds largely reached the lower intestinal tract. Upon administration of resveratrol, the major species found in this region was dihydroresveratrol, produced by enzymes of the intestinal flora. In experiments with a fully protected (trisubstituted) deoxygalactose containing prodrug, the major species were the prodrug itself and partially deprotected derivatives, along with small amounts of dihydroresveratrol. We conclude that the N-monosubstituted Carbamate moiety is suitable for use in prodrugs of polyphenols.
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New water-soluble Carbamate Ester derivatives of resveratrol.
Molecules (Basel Switzerland), 2014Co-Authors: Andrea Mattarei, Massimo Carraro, Michele Azzolini, Cristina Paradisi, Mario Zoratti, Lucia BiasuttoAbstract:Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism and can be exploited to modulate the physicochemical properties of the compound. We report here the synthesis and characterization of Carbamate Ester derivatives of resveratrol bearing on each nitrogen atom a methyl group and either a methoxy-poly(ethylene glycol)-350 (mPEG-350) or a butyl-glucosyl promoiety conferring high water solubility. Ex vivo absorption studies revealed that the butyl-glucosyl conjugate, unlike the mPEG-350 one, is able to permeate the intestinal wall. In vivo pharmacokinetics confirmed absorption after oral administration and showed that no hydrolysis of the Carbamate groups takes place. Thus, sugar groups can be attached to resveratrol to obtain soluble derivatives maintaining to some degree the ability to permeate biomembranes, perhaps by facilitated or active transport.
Ashgan Bishara - One of the best experts on this subject based on the ideXlab platform.
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Salarins A and B and Tulearin A: New Cytotoxic Sponge-Derived Macrolides
Organic Letters, 2008Co-Authors: Ashgan Bishara, Amira Rudi, Maurice Aknin, Drorit Neumann, Nathalie Ben-califa, Yoel KashmanAbstract:Three novel nitrogenous macrolides designated salarin A (e.g. I) and B (II) and tulearin A were isolated from the Madagascar Fascaplysinopsis sp. sponge. The structures of the compds. were elucidated by interpretation of MS and 1D and 2D NMR spectra. Both salarins carry an acetylCarbamate moiety, and in addn., I contains a triacylamine group and II a methoxymethylketone lactam. Tulearin A carries the naturally rare Carbamate Ester. The compds. were found to be toxic to brine shrimp larvae, and salarin A and tulearin A were also cytotoxic to leukemia cells. [on SciFinder(R)]
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Salarins a and B and tulearin a: new cytotoxic sponge-derived macrolides.
Organic letters, 2007Co-Authors: Ashgan Bishara, Amira Rudi, Maurice Aknin, Drorit Neumann, Nathalie Ben-califa, Yoel KashmanAbstract:Three novel nitrogenous macrolides designated salarin A and B (1 and 2) and tulearin A (3) were isolated from the Madagascar Fascaplysinopsis sp. sponge. The structures of the compounds were elucidated by interpretation of MS and 1D and 2D NMR spectra. Both salarins carry an acetylCarbamate moiety, and in addition, 1 contains a triacylamine group and 2 a methoxymethylketone lactam. Tulearin A carries the naturally rare Carbamate Ester. The compounds were found to be toxic to brine shrimp larvae, and salarin A and tulearin A were also cytotoxic to leukemia cells.
V.l. Furer - One of the best experts on this subject based on the ideXlab platform.
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DFT study of structure, IR and Raman spectra of the first generation dendron built from cyclotriphosphazene core with terminal Carbamate and Ester groups
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2012Co-Authors: V.l. Furer, A.e. Vandyukov, S. Fuchs, J.p. Majoral, A.m. Caminade, V.i. KovalenkoAbstract:The FTIR and FT-Raman spectra of the first generation dendron built from the cyclotriphosphazene core, five arms OC6H4CHNN(CH3)P(S) with ten Carbamate terminal groups and one Ester function Gv1 have been recorded. The IR and Raman spectra of the zero generation dendron Gv0 and first generation dendrimer G1 with the same core and terminal groups were also examined. The structural optimization and normal mode analysis were performed for dendron Gv1 on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that Gv1 has a concave lens structure with planar OC6H4CHNN(CH3)P(S) fragments and slightly non-planar cyclotriphosphazene core. The Carbamate groups attached to different arms show significant deviations from a symmetrical arrangement relative to the local planes of repeating units. The experimental IR spectrum of Gv1 dendron was interpreted by means of potential energy distributions. The strong band 1604 cm−1 shows marked changes of the optical density in dependence of the Carbamate, Ester or azomethyne substituents in the aromatic ring. The frequencies of ν(NH) and ν(CO) bands in the IR spectra reveal the presence of the different types of H-bonds in the studied dendrimers
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DFT study of structure, IR and Raman spectra of the first generation dendron built from cyclotriphosphazene core with terminal Carbamate and Ester groups.
Spectrochimica acta. Part A Molecular and biomolecular spectroscopy, 2012Co-Authors: V.l. Furer, A.e. Vandyukov, S. Fuchs, J.p. Majoral, A.m. Caminade, V.i. KovalenkoAbstract:The FTIR and FT-Raman spectra of the first generation dendron built from the cyclotriphosphazene core, five arms -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds on the righthand side with ten Carbamate terminal groups and one Ester function G(v1) have been recorded. The IR and Raman spectra of the zero generation dendron G(v0) and first generation dendrimer G(1) with the same core and terminal groups were also examined. The structural optimization and normal mode analysis were performed for dendron G(v1) on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that G(v1) has a concave lens structure with planar -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds on the righhand side fragments and slightly non-planar cyclotriphosphazene core. The Carbamate groups attached to different arms show significant deviations from a symmetrical arrangement relative to the local planes of repeating units. The experimental IR spectrum of G(v1) dendron was interpreted by means of potential energy distributions. The strong band 1604 cm(-1) shows marked changes of the optical density in dependence of the Carbamate, Ester or azomethyne substituents in the aromatic ring. The frequencies of ν(N-H) and ν(C=O) bands in the IR spectra reveal the presence of the different types of H-bonds in the studied dendrimers.