Cargando…

Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers

Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development...

Descripción completa

Detalles Bibliográficos
Autores principales: Ramirez, Daniela Andrea, Federici, María Fernanda, Altamirano, Jorgelina Cecilia, Camargo, Alejandra Beatriz, Luco, Juan María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488277/
https://www.ncbi.nlm.nih.gov/pubmed/34616711
http://dx.doi.org/10.3389/fchem.2021.690707
_version_ 1784578128272687104
author Ramirez, Daniela Andrea
Federici, María Fernanda
Altamirano, Jorgelina Cecilia
Camargo, Alejandra Beatriz
Luco, Juan María
author_facet Ramirez, Daniela Andrea
Federici, María Fernanda
Altamirano, Jorgelina Cecilia
Camargo, Alejandra Beatriz
Luco, Juan María
author_sort Ramirez, Daniela Andrea
collection PubMed
description Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of the said compounds once consumed, it is necessary to previously evaluate the ADME (absorption, distribution, metabolism, and excretion) profile. Alternatively, in vitro and in silico methods attempt to avoid or reduce experimental animals’ use and provide preliminary information on drugs’ ability to overcome the various biological barriers inherent in the ADME process. In this sense, in silico methods serve to provide primary information on drugs’ bioavailability mechanisms. High-performance liquid chromatography (HPLC) using a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds which are extensively used in studies of quantitative structure–activity relationships (QSARs). In the present study, the chromatographic capacity factors (log k’ (IAM)) for 28 OSCs were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, several quantitative structure–retention relationships (QSRRs) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds under study on IAM phases. As expected, the hydrophobic factors are of prime importance for the IAM retention of these compounds. However, the molecular flexibility and specific polar interactions expressed by several electronic descriptors (relative negative charge, RNCG, and Mulliken electronegativity) are also involved. We also evaluated the IAM phase ability to assess several ADME parameters for the OSCs under study obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace and the PreADMET web tool. The human gastrointestinal absorption (HIA), blood–brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k’(IAM), which provide evidence for the great potential of the IAM phases in the development of QSAR models.
format Online
Article
Text
id pubmed-8488277
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-84882772021-10-05 Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers Ramirez, Daniela Andrea Federici, María Fernanda Altamirano, Jorgelina Cecilia Camargo, Alejandra Beatriz Luco, Juan María Front Chem Chemistry Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of the said compounds once consumed, it is necessary to previously evaluate the ADME (absorption, distribution, metabolism, and excretion) profile. Alternatively, in vitro and in silico methods attempt to avoid or reduce experimental animals’ use and provide preliminary information on drugs’ ability to overcome the various biological barriers inherent in the ADME process. In this sense, in silico methods serve to provide primary information on drugs’ bioavailability mechanisms. High-performance liquid chromatography (HPLC) using a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds which are extensively used in studies of quantitative structure–activity relationships (QSARs). In the present study, the chromatographic capacity factors (log k’ (IAM)) for 28 OSCs were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, several quantitative structure–retention relationships (QSRRs) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds under study on IAM phases. As expected, the hydrophobic factors are of prime importance for the IAM retention of these compounds. However, the molecular flexibility and specific polar interactions expressed by several electronic descriptors (relative negative charge, RNCG, and Mulliken electronegativity) are also involved. We also evaluated the IAM phase ability to assess several ADME parameters for the OSCs under study obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace and the PreADMET web tool. The human gastrointestinal absorption (HIA), blood–brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k’(IAM), which provide evidence for the great potential of the IAM phases in the development of QSAR models. Frontiers Media S.A. 2021-09-20 /pmc/articles/PMC8488277/ /pubmed/34616711 http://dx.doi.org/10.3389/fchem.2021.690707 Text en Copyright © 2021 Ramirez, Federici, Altamirano, Camargo and Luco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Ramirez, Daniela Andrea
Federici, María Fernanda
Altamirano, Jorgelina Cecilia
Camargo, Alejandra Beatriz
Luco, Juan María
Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers
title Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers
title_full Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers
title_fullStr Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers
title_full_unstemmed Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers
title_short Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers
title_sort permeability data of organosulfur garlic compounds estimated by immobilized artificial membrane chromatography: correlation across several biological barriers
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488277/
https://www.ncbi.nlm.nih.gov/pubmed/34616711
http://dx.doi.org/10.3389/fchem.2021.690707
work_keys_str_mv AT ramirezdanielaandrea permeabilitydataoforganosulfurgarliccompoundsestimatedbyimmobilizedartificialmembranechromatographycorrelationacrossseveralbiologicalbarriers
AT federicimariafernanda permeabilitydataoforganosulfurgarliccompoundsestimatedbyimmobilizedartificialmembranechromatographycorrelationacrossseveralbiologicalbarriers
AT altamiranojorgelinacecilia permeabilitydataoforganosulfurgarliccompoundsestimatedbyimmobilizedartificialmembranechromatographycorrelationacrossseveralbiologicalbarriers
AT camargoalejandrabeatriz permeabilitydataoforganosulfurgarliccompoundsestimatedbyimmobilizedartificialmembranechromatographycorrelationacrossseveralbiologicalbarriers
AT lucojuanmaria permeabilitydataoforganosulfurgarliccompoundsestimatedbyimmobilizedartificialmembranechromatographycorrelationacrossseveralbiologicalbarriers