Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia

Claudia Pérez, José Becerra, Paula Manríquez-Navarro, Luis Gerardo Aguayo, Jorge Fuentealba, José Leonardo Guzmán, Pedro Joseph-Nathan, Verónica Jiménez, Marcelo Andrés Muñoz, Mario Silva

Resultado de la investigación: Article

4 Citas (Scopus)

Resumen

The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native γ-aminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the lactone at carbons 3 and 5, the presence of the hydroxyl group at position 6, and the different electronic distributions observed in tutin and coriamyrtin. The latter has an isopropenyl moiety at carbon 4 in contrast to the dihydrotutin isopropyl group at the same position, which could explain the difference in activity between dihydrotutin and tutin or coriamyrtin. The presence of the hydroxyl group at carbon 2 is not decisive since this functionality is present in tutin, the most active compound, and in dihydrotutin, the less active one.

Idioma originalEnglish
Páginas (desde-hasta)161-165
Número de páginas5
PublicaciónChemical and Pharmaceutical Bulletin
Volumen59
N.º2
DOI
EstadoPublished - 1 feb 2011

Huella dactilar

Sesquiterpenes
Neurology
Central Nervous System
Carbon
Lactones
Hydroxyl Radical
Neurons
Aminobutyrates
Molecular Conformation
Picrotoxin
Metabolites
Circular Dichroism
Static Electricity
gamma-Aminobutyric Acid
Electron energy levels
Rats
Electrostatics
Software
tutin
coriaria lactone

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

Citar esto

Pérez, Claudia ; Becerra, José ; Manríquez-Navarro, Paula ; Aguayo, Luis Gerardo ; Fuentealba, Jorge ; Guzmán, José Leonardo ; Joseph-Nathan, Pedro ; Jiménez, Verónica ; Muñoz, Marcelo Andrés ; Silva, Mario. / Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia. En: Chemical and Pharmaceutical Bulletin. 2011 ; Vol. 59, N.º 2. pp. 161-165.
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title = "Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia",
abstract = "The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native γ-aminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the lactone at carbons 3 and 5, the presence of the hydroxyl group at position 6, and the different electronic distributions observed in tutin and coriamyrtin. The latter has an isopropenyl moiety at carbon 4 in contrast to the dihydrotutin isopropyl group at the same position, which could explain the difference in activity between dihydrotutin and tutin or coriamyrtin. The presence of the hydroxyl group at carbon 2 is not decisive since this functionality is present in tutin, the most active compound, and in dihydrotutin, the less active one.",
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author = "Claudia P{\'e}rez and Jos{\'e} Becerra and Paula Manr{\'i}quez-Navarro and Aguayo, {Luis Gerardo} and Jorge Fuentealba and Guzm{\'a}n, {Jos{\'e} Leonardo} and Pedro Joseph-Nathan and Ver{\'o}nica Jim{\'e}nez and Mu{\~n}oz, {Marcelo Andr{\'e}s} and Mario Silva",
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Pérez, C, Becerra, J, Manríquez-Navarro, P, Aguayo, LG, Fuentealba, J, Guzmán, JL, Joseph-Nathan, P, Jiménez, V, Muñoz, MA & Silva, M 2011, 'Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia', Chemical and Pharmaceutical Bulletin, vol. 59, n.º 2, pp. 161-165. https://doi.org/10.1248/cpb.59.161

Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia. / Pérez, Claudia; Becerra, José; Manríquez-Navarro, Paula; Aguayo, Luis Gerardo; Fuentealba, Jorge; Guzmán, José Leonardo; Joseph-Nathan, Pedro; Jiménez, Verónica; Muñoz, Marcelo Andrés; Silva, Mario.

En: Chemical and Pharmaceutical Bulletin, Vol. 59, N.º 2, 01.02.2011, p. 161-165.

Resultado de la investigación: Article

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T1 - Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia

AU - Pérez, Claudia

AU - Becerra, José

AU - Manríquez-Navarro, Paula

AU - Aguayo, Luis Gerardo

AU - Fuentealba, Jorge

AU - Guzmán, José Leonardo

AU - Joseph-Nathan, Pedro

AU - Jiménez, Verónica

AU - Muñoz, Marcelo Andrés

AU - Silva, Mario

PY - 2011/2/1

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N2 - The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native γ-aminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the lactone at carbons 3 and 5, the presence of the hydroxyl group at position 6, and the different electronic distributions observed in tutin and coriamyrtin. The latter has an isopropenyl moiety at carbon 4 in contrast to the dihydrotutin isopropyl group at the same position, which could explain the difference in activity between dihydrotutin and tutin or coriamyrtin. The presence of the hydroxyl group at carbon 2 is not decisive since this functionality is present in tutin, the most active compound, and in dihydrotutin, the less active one.

AB - The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native γ-aminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the lactone at carbons 3 and 5, the presence of the hydroxyl group at position 6, and the different electronic distributions observed in tutin and coriamyrtin. The latter has an isopropenyl moiety at carbon 4 in contrast to the dihydrotutin isopropyl group at the same position, which could explain the difference in activity between dihydrotutin and tutin or coriamyrtin. The presence of the hydroxyl group at carbon 2 is not decisive since this functionality is present in tutin, the most active compound, and in dihydrotutin, the less active one.

KW - Coriamyrtin

KW - Dihydrotutin

KW - Picrotoxin compound

KW - Tutin

KW - Vibrational circular dichroism

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DO - 10.1248/cpb.59.161

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