Apurba Dutta - Academia.edu (original) (raw)
Papers by Apurba Dutta
The Journal of Organic Chemistry, 2005
The Journal of Organic Chemistry, 1990
The Journal of Organic Chemistry, 2008
The Journal of Organic Chemistry, 2001
Four new D-secopaclitaxel analogues were synthesized from paclitaxel. The key step of the synthes... more Four new D-secopaclitaxel analogues were synthesized from paclitaxel. The key step of the synthesis involved the opening of the D-ring by Jones oxidation. Two of the compounds had been predicted to be nearly as active as paclitaxel in a minireceptor model of the binding site on tubulin, but all were biologically inactive in an in vitro cytotoxic assay and a tubulin assembly assay. The biological results identify a weakness in our predictive minireceptor model and suggest a corrective remedy in which additional amino acids are needed to accommodate ligand-protein steric effects around the oxetane ring. These changes to the model lead to correct predictions of the bioactivity. Conformational analysis and dynamics simulations of the compounds showed that the 4-acetyl substituent is as important as the oxetane in determining the A ring conformation.
Journal of Medicinal Chemistry, 2010
Journal of Medicinal Chemistry, 2005
Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram... more Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a series of acylated homologated spermine compounds with lipopolysaccharide (LPS) have been characterized. The optimal acyl chain length for effective sequestration of LPS was identified to be C 16 for the mono-acyl compounds. The most promising of these compounds, 4e, binds LPS with an ED 50 of 1.37 μM. Nitric oxide production in murine J774A.1 cells, as well as TNF-α in human blood, are inhibited in a dose-dependent manner by 4e at concentrations orders of magnitude lower than toxic doses. Administration of 4e to D-galactosamine-sensitized mice challenged with supralethal doses of LPS provided significant protection against lethality. Potent anti-endotoxic activity, low toxicity, and ease of synthesis render this class of compounds candidate endotoxin-sequestering agents of potential significant therapeutic value.
Journal of Neurochemistry, 2015
The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters ... more The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters and NMDA receptors. Both enantiomers inhibited glutamate transporters in rat hippocampal crude synaptosomes and elicited substrate-like activity at excitatory amino acid transporter 1, 2, and 3 as measured by voltage clamp in the Xenopus oocyte expression system. The enantiomers had similar affinities, but the D-enantiomer showed a lower maximal effect at excitatory amino acid transporter 1, 2, and 3 than the L-enantiomer. Surprisingly, D-erythro-3-hydroxyaspartate was a potent NMDA receptor agonist with an EC 50 value in rat hippocampal neurons of 320 nM, whereas the L-enantiomer was 100-fold less potent. L-erythro-3-hydroxyaspartate showed activity at both glutamate transporters and NMDA receptors at concentrations that are reported to inhibit serine racemase, indicating a lack of selectivity. This enantiomeric pair may assist in shedding further light on the structural requirements for substrate activity at glutamate transporters and for agonist activity at NMDA receptors.
Journal of the Chemical Society, Perkin Transactions 1, 1984
ABSTRACT The ketene dithioacetal (7) derived from indan-1-one gave a dimeric product (8) on treat... more ABSTRACT The ketene dithioacetal (7) derived from indan-1-one gave a dimeric product (8) on treatment with sodium hydride in dimethylformamide under nitrogen. The dithioacetal (15) derived from 1-tetralone on prolonged treatment with sodium hydride under identical conditions yielded the corresponding methyl β-oxodithioester (16) and the S-methyl β-oxothioester (17). Under similar conditions, the dithioacetal (28) derived from 2,3-dihydro-1-benzothiopyran-4-one gave the expected rearranged product (29) formed by a 1,3-methylthio shift. The structural assignments of the products (8), (16), (17), and (29) and the probable mechanism for the formation of (8), (16), and (17) are described.
Tetrahedron Letters, 1997
A stereodefined synthesis of both the C-3 isomers of the title tyrosine related new amino acid 3 ... more A stereodefined synthesis of both the C-3 isomers of the title tyrosine related new amino acid 3 has been achieved starting from D-serine and 4-bromophenol.
Tetrahedron Letters, 1988
ABSTRACT
Tetrahedron Letters, 1994
Hydrolytic procedures for selective 2-debenzoylation and 2,4dideacylation of 2-O-&rrt-butyldimeth... more Hydrolytic procedures for selective 2-debenzoylation and 2,4dideacylation of 2-O-&rrt-butyldimethylsilyl-7-0-(triethylsilyl)taxol are reported. The fast synthesis and biological evaluation of a Qsubstituted analogue, 4-deacetyl-4-isobutauoyltaxol, is presented. The chemistry described in this letter is suitable for the facile synthesis of tax01 congeners modified at C-2 and/or C-4.
Tetrahedron Letters, 1998
An efficient synthesis of the widely used antibiotic chloramphenicol (1) is described. The key st... more An efficient synthesis of the widely used antibiotic chloramphenicol (1) is described. The key step in the synthesis involves chelation-controlled addition of phenylmagnesium bromide to a suitably protected D-serinal derivative, affording the pivotal D-threo 1,2-amino alcohol intenn~ate 3 in a highly stereoselective manner.
Tetrahedron Letters, 1992
Abstract A short practical method for the enantioselective synthesis of (−)-vertinolide precursor... more Abstract A short practical method for the enantioselective synthesis of (−)-vertinolide precursor 2 is described. The readily available chiral β-alkoxy substituted acrylate 7 has been reacted with the ethyl levulinate to form the tetronic acid nucleus 8, which in three subsequent steps was converted to the known precursor 2 in high overall yield.
Tetrahedron Letters, 1993
Abstract A one step synthesis of highly functionalized cyclopentenones has been developed by the ... more Abstract A one step synthesis of highly functionalized cyclopentenones has been developed by the Michael addition of the readily available β-lithiated acrylate 1A with suitable acceptors.
Tetrahedron Letters, 2005
Utilizing an L L-serine derived enantiopure aminobutenolide as a chiral template, an efficient sy... more Utilizing an L L-serine derived enantiopure aminobutenolide as a chiral template, an efficient synthesis of a doubly modified novel biotin analog has been achieved. In view of the renewed interest in understanding the various biological roles of biotin, the title analog could provide some as yet unreported structure-activity relationship information on this important vitamin.
Tetrahedron, 1998
Penelitian ini bertujuan untuk menganalisis pengaruh kualitas pelayanan dan kepuasan pelanggan te... more Penelitian ini bertujuan untuk menganalisis pengaruh kualitas pelayanan dan kepuasan pelanggan terhadap keputusan pembelian tiket kereta api. Penelitian ini merupakan penelitian explanatory research. Populasi penelitian ini adalah mahasiswa Program Studi D4 Manajemen Pemasaran Jurusan Administrasi Niaga Politeknik Negeri Malang Tahun Akademik 2017/2018 pelanggan jasa kereta api. Data dikumpulkan dengan cara menyebar kuesioner kepada 80 responden menggunakan teknik sampling jenuh. Analisa data yang digunakan adalah regresi linier berganda, uji t, serta uji F. Hasil penelitian ini menunjukkan bahwa variabel keputusan pembelian dapat dijelaskan oleh variabel kualitas pelayanan dan kepuasan pelanggan sebesar 84%. Sedangkan sisanya oleh variabel lain yang tidak dimasukkan dalam penelitian ini. Kata-kata kunci: kualitas pelayanan, kepuasan pelanggan, keputusan pembelian, PT Kereta Api Indonesia (Persero)
Molecular Pharmaceutics, 2008
Hydrophobically substituted polyamine compounds, particularly N-acyl or N-alkyl derivatives of ho... more Hydrophobically substituted polyamine compounds, particularly N-acyl or N-alkyl derivatives of homospermine, are potent endotoxin (lipopolysaccharide) sequestrants. Despite their polycationic nature, the aqueous solubilites are limited owing to the considerable overall hydrophobicity contributed by the long-chain aliphatic substituent, but solubilization is readily achieved in the presence of human serum albumin (HSA). We desired first to delineate the structural basis of lipopolyamine-albumin interactions and, second, to explore possible structure-activity correlates in a well-defined, congeneric series of N-alkyl and-acyl homospermine lead compounds. Fluorescence spectroscopic and isothermal titration calorimetry (ITC) results indicate that these compounds appear to bind to HSA via occupancy of the fatty-acid binding sites on the protein. The acyl and carbamate compounds bind HSA the strongest; the ureido and N-alkyl analogues are significantly weaker, and the branched alkyl compound is weaker still. ITC-derived dissociation constants are weighted almost in their entirety by enthalpic ∆H terms, which is suggestive that the polarizability of the carbonyl groups facilitate, at least in large part, their interactions with HSA. The relative affinities of these lipopolyamines toward HSA is reflected in discernible differences in apparent potencies of LPS-sequestering activity under experimental conditions requiring physiological concentrations of HSA, and also of in vivo pharmacodynamic behavior. These results are likely to be useful in designing analogues with varying pharmacokinetic profiles.
The Journal of Organic Chemistry, 2001
The Journal of Organic Chemistry, 2005
The Journal of Organic Chemistry, 1990
The Journal of Organic Chemistry, 2008
The Journal of Organic Chemistry, 2001
Four new D-secopaclitaxel analogues were synthesized from paclitaxel. The key step of the synthes... more Four new D-secopaclitaxel analogues were synthesized from paclitaxel. The key step of the synthesis involved the opening of the D-ring by Jones oxidation. Two of the compounds had been predicted to be nearly as active as paclitaxel in a minireceptor model of the binding site on tubulin, but all were biologically inactive in an in vitro cytotoxic assay and a tubulin assembly assay. The biological results identify a weakness in our predictive minireceptor model and suggest a corrective remedy in which additional amino acids are needed to accommodate ligand-protein steric effects around the oxetane ring. These changes to the model lead to correct predictions of the bioactivity. Conformational analysis and dynamics simulations of the compounds showed that the 4-acetyl substituent is as important as the oxetane in determining the A ring conformation.
Journal of Medicinal Chemistry, 2010
Journal of Medicinal Chemistry, 2005
Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram... more Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a series of acylated homologated spermine compounds with lipopolysaccharide (LPS) have been characterized. The optimal acyl chain length for effective sequestration of LPS was identified to be C 16 for the mono-acyl compounds. The most promising of these compounds, 4e, binds LPS with an ED 50 of 1.37 μM. Nitric oxide production in murine J774A.1 cells, as well as TNF-α in human blood, are inhibited in a dose-dependent manner by 4e at concentrations orders of magnitude lower than toxic doses. Administration of 4e to D-galactosamine-sensitized mice challenged with supralethal doses of LPS provided significant protection against lethality. Potent anti-endotoxic activity, low toxicity, and ease of synthesis render this class of compounds candidate endotoxin-sequestering agents of potential significant therapeutic value.
Journal of Neurochemistry, 2015
The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters ... more The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters and NMDA receptors. Both enantiomers inhibited glutamate transporters in rat hippocampal crude synaptosomes and elicited substrate-like activity at excitatory amino acid transporter 1, 2, and 3 as measured by voltage clamp in the Xenopus oocyte expression system. The enantiomers had similar affinities, but the D-enantiomer showed a lower maximal effect at excitatory amino acid transporter 1, 2, and 3 than the L-enantiomer. Surprisingly, D-erythro-3-hydroxyaspartate was a potent NMDA receptor agonist with an EC 50 value in rat hippocampal neurons of 320 nM, whereas the L-enantiomer was 100-fold less potent. L-erythro-3-hydroxyaspartate showed activity at both glutamate transporters and NMDA receptors at concentrations that are reported to inhibit serine racemase, indicating a lack of selectivity. This enantiomeric pair may assist in shedding further light on the structural requirements for substrate activity at glutamate transporters and for agonist activity at NMDA receptors.
Journal of the Chemical Society, Perkin Transactions 1, 1984
ABSTRACT The ketene dithioacetal (7) derived from indan-1-one gave a dimeric product (8) on treat... more ABSTRACT The ketene dithioacetal (7) derived from indan-1-one gave a dimeric product (8) on treatment with sodium hydride in dimethylformamide under nitrogen. The dithioacetal (15) derived from 1-tetralone on prolonged treatment with sodium hydride under identical conditions yielded the corresponding methyl β-oxodithioester (16) and the S-methyl β-oxothioester (17). Under similar conditions, the dithioacetal (28) derived from 2,3-dihydro-1-benzothiopyran-4-one gave the expected rearranged product (29) formed by a 1,3-methylthio shift. The structural assignments of the products (8), (16), (17), and (29) and the probable mechanism for the formation of (8), (16), and (17) are described.
Tetrahedron Letters, 1997
A stereodefined synthesis of both the C-3 isomers of the title tyrosine related new amino acid 3 ... more A stereodefined synthesis of both the C-3 isomers of the title tyrosine related new amino acid 3 has been achieved starting from D-serine and 4-bromophenol.
Tetrahedron Letters, 1988
ABSTRACT
Tetrahedron Letters, 1994
Hydrolytic procedures for selective 2-debenzoylation and 2,4dideacylation of 2-O-&rrt-butyldimeth... more Hydrolytic procedures for selective 2-debenzoylation and 2,4dideacylation of 2-O-&rrt-butyldimethylsilyl-7-0-(triethylsilyl)taxol are reported. The fast synthesis and biological evaluation of a Qsubstituted analogue, 4-deacetyl-4-isobutauoyltaxol, is presented. The chemistry described in this letter is suitable for the facile synthesis of tax01 congeners modified at C-2 and/or C-4.
Tetrahedron Letters, 1998
An efficient synthesis of the widely used antibiotic chloramphenicol (1) is described. The key st... more An efficient synthesis of the widely used antibiotic chloramphenicol (1) is described. The key step in the synthesis involves chelation-controlled addition of phenylmagnesium bromide to a suitably protected D-serinal derivative, affording the pivotal D-threo 1,2-amino alcohol intenn~ate 3 in a highly stereoselective manner.
Tetrahedron Letters, 1992
Abstract A short practical method for the enantioselective synthesis of (−)-vertinolide precursor... more Abstract A short practical method for the enantioselective synthesis of (−)-vertinolide precursor 2 is described. The readily available chiral β-alkoxy substituted acrylate 7 has been reacted with the ethyl levulinate to form the tetronic acid nucleus 8, which in three subsequent steps was converted to the known precursor 2 in high overall yield.
Tetrahedron Letters, 1993
Abstract A one step synthesis of highly functionalized cyclopentenones has been developed by the ... more Abstract A one step synthesis of highly functionalized cyclopentenones has been developed by the Michael addition of the readily available β-lithiated acrylate 1A with suitable acceptors.
Tetrahedron Letters, 2005
Utilizing an L L-serine derived enantiopure aminobutenolide as a chiral template, an efficient sy... more Utilizing an L L-serine derived enantiopure aminobutenolide as a chiral template, an efficient synthesis of a doubly modified novel biotin analog has been achieved. In view of the renewed interest in understanding the various biological roles of biotin, the title analog could provide some as yet unreported structure-activity relationship information on this important vitamin.
Tetrahedron, 1998
Penelitian ini bertujuan untuk menganalisis pengaruh kualitas pelayanan dan kepuasan pelanggan te... more Penelitian ini bertujuan untuk menganalisis pengaruh kualitas pelayanan dan kepuasan pelanggan terhadap keputusan pembelian tiket kereta api. Penelitian ini merupakan penelitian explanatory research. Populasi penelitian ini adalah mahasiswa Program Studi D4 Manajemen Pemasaran Jurusan Administrasi Niaga Politeknik Negeri Malang Tahun Akademik 2017/2018 pelanggan jasa kereta api. Data dikumpulkan dengan cara menyebar kuesioner kepada 80 responden menggunakan teknik sampling jenuh. Analisa data yang digunakan adalah regresi linier berganda, uji t, serta uji F. Hasil penelitian ini menunjukkan bahwa variabel keputusan pembelian dapat dijelaskan oleh variabel kualitas pelayanan dan kepuasan pelanggan sebesar 84%. Sedangkan sisanya oleh variabel lain yang tidak dimasukkan dalam penelitian ini. Kata-kata kunci: kualitas pelayanan, kepuasan pelanggan, keputusan pembelian, PT Kereta Api Indonesia (Persero)
Molecular Pharmaceutics, 2008
Hydrophobically substituted polyamine compounds, particularly N-acyl or N-alkyl derivatives of ho... more Hydrophobically substituted polyamine compounds, particularly N-acyl or N-alkyl derivatives of homospermine, are potent endotoxin (lipopolysaccharide) sequestrants. Despite their polycationic nature, the aqueous solubilites are limited owing to the considerable overall hydrophobicity contributed by the long-chain aliphatic substituent, but solubilization is readily achieved in the presence of human serum albumin (HSA). We desired first to delineate the structural basis of lipopolyamine-albumin interactions and, second, to explore possible structure-activity correlates in a well-defined, congeneric series of N-alkyl and-acyl homospermine lead compounds. Fluorescence spectroscopic and isothermal titration calorimetry (ITC) results indicate that these compounds appear to bind to HSA via occupancy of the fatty-acid binding sites on the protein. The acyl and carbamate compounds bind HSA the strongest; the ureido and N-alkyl analogues are significantly weaker, and the branched alkyl compound is weaker still. ITC-derived dissociation constants are weighted almost in their entirety by enthalpic ∆H terms, which is suggestive that the polarizability of the carbonyl groups facilitate, at least in large part, their interactions with HSA. The relative affinities of these lipopolyamines toward HSA is reflected in discernible differences in apparent potencies of LPS-sequestering activity under experimental conditions requiring physiological concentrations of HSA, and also of in vivo pharmacodynamic behavior. These results are likely to be useful in designing analogues with varying pharmacokinetic profiles.
The Journal of Organic Chemistry, 2001