Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids. / Conti, Paola; De Amici, Marco; Grazioso, Giovanni; Roda, Gabriella; Pinto, Andrea; Hansen, Kasper Bø; Nielsen, Birgitte; Madsen, Ulf; Bräuner-Osborne, Hans; Egebjerg, Jan; Vestri, Valentina; Pellegrini-Giampietro, Domenico E; Sibille, Pauline; Acher, Francine C; De Micheli, Carlo.

In: Journal of Medicinal Chemistry, Vol. 48, No. 20, 06.10.2005, p. 6315-25.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Conti, P, De Amici, M, Grazioso, G, Roda, G, Pinto, A, Hansen, KB, Nielsen, B, Madsen, U, Bräuner-Osborne, H, Egebjerg, J, Vestri, V, Pellegrini-Giampietro, DE, Sibille, P, Acher, FC & De Micheli, C 2005, 'Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids', Journal of Medicinal Chemistry, vol. 48, no. 20, pp. 6315-25. https://doi.org/10.1021/jm0504499

APA

Conti, P., De Amici, M., Grazioso, G., Roda, G., Pinto, A., Hansen, K. B., Nielsen, B., Madsen, U., Bräuner-Osborne, H., Egebjerg, J., Vestri, V., Pellegrini-Giampietro, D. E., Sibille, P., Acher, F. C., & De Micheli, C. (2005). Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids. Journal of Medicinal Chemistry, 48(20), 6315-25. https://doi.org/10.1021/jm0504499

Vancouver

Conti P, De Amici M, Grazioso G, Roda G, Pinto A, Hansen KB et al. Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids. Journal of Medicinal Chemistry. 2005 Oct 6;48(20):6315-25. https://doi.org/10.1021/jm0504499

Author

Conti, Paola ; De Amici, Marco ; Grazioso, Giovanni ; Roda, Gabriella ; Pinto, Andrea ; Hansen, Kasper Bø ; Nielsen, Birgitte ; Madsen, Ulf ; Bräuner-Osborne, Hans ; Egebjerg, Jan ; Vestri, Valentina ; Pellegrini-Giampietro, Domenico E ; Sibille, Pauline ; Acher, Francine C ; De Micheli, Carlo. / Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids. In: Journal of Medicinal Chemistry. 2005 ; Vol. 48, No. 20. pp. 6315-25.

Bibtex

@article{9fc111e2e49f44fcb50cac4b0e45b64d,
title = "Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids",
abstract = "The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis of two pairs of enantiomers, which were subsequently resolved by enzymatic procedures. These four stereoisomers and the four stereoisomers of the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, and (-)-3 were tested at ionotropic and metabotropic glutamate receptor subtypes. The most potent NMDA receptor antagonists [(+)-2, (-)-4, and (+)-5] showed a significant neuroprotective effect when tested in an oxygen glucose deprivation (OGD) cell culture test. The same compounds were preliminarily assayed using Xenopus oocytes expressing cloned rat NMDA receptors containing the NR1 subunit in combination with either NR2A, NR2B, NR2C, or NR2D subunit. In this assay, all three derivatives showed high antagonist potency with preference for the NR2A and NR2B subtypes, with derivative (-)-4 behaving as the most potent antagonist. The biological data are discussed on the basis of homology models reported in the literature for NMDA receptors and mGluRs.",
keywords = "Amino Acids, Animals, Binding Sites, CHO Cells, Cells, Cultured, Cerebral Cortex, Cricetinae, Cricetulus, Female, Isoxazoles, Mice, Models, Molecular, Neuroprotective Agents, Oocytes, Patch-Clamp Techniques, Protein Subunits, Radioligand Assay, Rats, Receptors, Glutamate, Receptors, Metabotropic Glutamate, Receptors, N-Methyl-D-Aspartate, Second Messenger Systems, Stereoisomerism, Structure-Activity Relationship, Xenopus laevis",
author = "Paola Conti and {De Amici}, Marco and Giovanni Grazioso and Gabriella Roda and Andrea Pinto and Hansen, {Kasper B{\o}} and Birgitte Nielsen and Ulf Madsen and Hans Br{\"a}uner-Osborne and Jan Egebjerg and Valentina Vestri and Pellegrini-Giampietro, {Domenico E} and Pauline Sibille and Acher, {Francine C} and {De Micheli}, Carlo",
year = "2005",
month = oct,
day = "6",
doi = "10.1021/jm0504499",
language = "English",
volume = "48",
pages = "6315--25",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "20",

}

RIS

TY - JOUR

T1 - Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids

AU - Conti, Paola

AU - De Amici, Marco

AU - Grazioso, Giovanni

AU - Roda, Gabriella

AU - Pinto, Andrea

AU - Hansen, Kasper Bø

AU - Nielsen, Birgitte

AU - Madsen, Ulf

AU - Bräuner-Osborne, Hans

AU - Egebjerg, Jan

AU - Vestri, Valentina

AU - Pellegrini-Giampietro, Domenico E

AU - Sibille, Pauline

AU - Acher, Francine C

AU - De Micheli, Carlo

PY - 2005/10/6

Y1 - 2005/10/6

N2 - The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis of two pairs of enantiomers, which were subsequently resolved by enzymatic procedures. These four stereoisomers and the four stereoisomers of the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, and (-)-3 were tested at ionotropic and metabotropic glutamate receptor subtypes. The most potent NMDA receptor antagonists [(+)-2, (-)-4, and (+)-5] showed a significant neuroprotective effect when tested in an oxygen glucose deprivation (OGD) cell culture test. The same compounds were preliminarily assayed using Xenopus oocytes expressing cloned rat NMDA receptors containing the NR1 subunit in combination with either NR2A, NR2B, NR2C, or NR2D subunit. In this assay, all three derivatives showed high antagonist potency with preference for the NR2A and NR2B subtypes, with derivative (-)-4 behaving as the most potent antagonist. The biological data are discussed on the basis of homology models reported in the literature for NMDA receptors and mGluRs.

AB - The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis of two pairs of enantiomers, which were subsequently resolved by enzymatic procedures. These four stereoisomers and the four stereoisomers of the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, and (-)-3 were tested at ionotropic and metabotropic glutamate receptor subtypes. The most potent NMDA receptor antagonists [(+)-2, (-)-4, and (+)-5] showed a significant neuroprotective effect when tested in an oxygen glucose deprivation (OGD) cell culture test. The same compounds were preliminarily assayed using Xenopus oocytes expressing cloned rat NMDA receptors containing the NR1 subunit in combination with either NR2A, NR2B, NR2C, or NR2D subunit. In this assay, all three derivatives showed high antagonist potency with preference for the NR2A and NR2B subtypes, with derivative (-)-4 behaving as the most potent antagonist. The biological data are discussed on the basis of homology models reported in the literature for NMDA receptors and mGluRs.

KW - Amino Acids

KW - Animals

KW - Binding Sites

KW - CHO Cells

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Cricetinae

KW - Cricetulus

KW - Female

KW - Isoxazoles

KW - Mice

KW - Models, Molecular

KW - Neuroprotective Agents

KW - Oocytes

KW - Patch-Clamp Techniques

KW - Protein Subunits

KW - Radioligand Assay

KW - Rats

KW - Receptors, Glutamate

KW - Receptors, Metabotropic Glutamate

KW - Receptors, N-Methyl-D-Aspartate

KW - Second Messenger Systems

KW - Stereoisomerism

KW - Structure-Activity Relationship

KW - Xenopus laevis

U2 - 10.1021/jm0504499

DO - 10.1021/jm0504499

M3 - Journal article

C2 - 16190758

VL - 48

SP - 6315

EP - 6325

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 20

ER -

ID: 45613671