On the Rational Drug Design for Hypertension through NMR Spectroscopy
Antagonists of the AT1receptor (AT1R) are beneficial molecules that can prevent the peptide hormone angiotensin II from binding and activating the specific receptor causing hypertension in pathological states. This review article summarizes the multifaced applications of solid and liquid state high...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-12-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/26/1/12 |
id |
doaj-1572e33f053544ba9ca44020c5d8e9ac |
---|---|
record_format |
Article |
spelling |
doaj-1572e33f053544ba9ca44020c5d8e9ac2020-12-23T00:04:03ZengMDPI AGMolecules1420-30492021-12-0126121210.3390/molecules26010012On the Rational Drug Design for Hypertension through NMR SpectroscopyEleni Chontzopoulou0Andreas G. Tzakos1Thomas Mavromoustakos2Department of Chemistry, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, GreeceDepartment of Chemistry, National and Kapodistrian University of Athens, 15784 Athens, GreeceAntagonists of the AT1receptor (AT1R) are beneficial molecules that can prevent the peptide hormone angiotensin II from binding and activating the specific receptor causing hypertension in pathological states. This review article summarizes the multifaced applications of solid and liquid state high resolution nuclear magnetic resonance (NMR) spectroscopy in antihypertensive commercial drugs that act as AT1R antagonists. The 3D architecture of these compounds is explored through 2D NOESY spectroscopy and their interactions with micelles and lipid bilayers are described using solid state <sup>13</sup>CP/MAS, <sup>31</sup>P and <sup>2</sup>H static solid state NMR spectroscopy. Due to their hydrophobic character, AT1R antagonists do not exert their optimum profile on the AT1R. Therefore, various vehicles are explored so as to effectively deliver these molecules to the site of action and to enhance their pharmaceutical efficacy. Cyclodextrins and polymers comprise successful examples of effective drug delivery vehicles, widely used for the delivery of hydrophobic drugs to the active site of the receptor. High resolution NMR spectroscopy provides valuable information on the physical-chemical forces that govern these drug:vehicle interactions, knowledge required to get a deeper understanding on the stability of the formed complexes and therefore the appropriateness and usefulness of the drug delivery system. In addition, it provides valuable information on the rational design towards the synthesis of more stable and efficient drug formulations.https://www.mdpi.com/1420-3049/26/1/12NMR spectroscopyAT1R antagonistslipid bilayersconformational propertiesdrug formulationpolymers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eleni Chontzopoulou Andreas G. Tzakos Thomas Mavromoustakos |
spellingShingle |
Eleni Chontzopoulou Andreas G. Tzakos Thomas Mavromoustakos On the Rational Drug Design for Hypertension through NMR Spectroscopy Molecules NMR spectroscopy AT1R antagonists lipid bilayers conformational properties drug formulation polymers |
author_facet |
Eleni Chontzopoulou Andreas G. Tzakos Thomas Mavromoustakos |
author_sort |
Eleni Chontzopoulou |
title |
On the Rational Drug Design for Hypertension through NMR Spectroscopy |
title_short |
On the Rational Drug Design for Hypertension through NMR Spectroscopy |
title_full |
On the Rational Drug Design for Hypertension through NMR Spectroscopy |
title_fullStr |
On the Rational Drug Design for Hypertension through NMR Spectroscopy |
title_full_unstemmed |
On the Rational Drug Design for Hypertension through NMR Spectroscopy |
title_sort |
on the rational drug design for hypertension through nmr spectroscopy |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-12-01 |
description |
Antagonists of the AT1receptor (AT1R) are beneficial molecules that can prevent the peptide hormone angiotensin II from binding and activating the specific receptor causing hypertension in pathological states. This review article summarizes the multifaced applications of solid and liquid state high resolution nuclear magnetic resonance (NMR) spectroscopy in antihypertensive commercial drugs that act as AT1R antagonists. The 3D architecture of these compounds is explored through 2D NOESY spectroscopy and their interactions with micelles and lipid bilayers are described using solid state <sup>13</sup>CP/MAS, <sup>31</sup>P and <sup>2</sup>H static solid state NMR spectroscopy. Due to their hydrophobic character, AT1R antagonists do not exert their optimum profile on the AT1R. Therefore, various vehicles are explored so as to effectively deliver these molecules to the site of action and to enhance their pharmaceutical efficacy. Cyclodextrins and polymers comprise successful examples of effective drug delivery vehicles, widely used for the delivery of hydrophobic drugs to the active site of the receptor. High resolution NMR spectroscopy provides valuable information on the physical-chemical forces that govern these drug:vehicle interactions, knowledge required to get a deeper understanding on the stability of the formed complexes and therefore the appropriateness and usefulness of the drug delivery system. In addition, it provides valuable information on the rational design towards the synthesis of more stable and efficient drug formulations. |
topic |
NMR spectroscopy AT1R antagonists lipid bilayers conformational properties drug formulation polymers |
url |
https://www.mdpi.com/1420-3049/26/1/12 |
work_keys_str_mv |
AT elenichontzopoulou ontherationaldrugdesignforhypertensionthroughnmrspectroscopy AT andreasgtzakos ontherationaldrugdesignforhypertensionthroughnmrspectroscopy AT thomasmavromoustakos ontherationaldrugdesignforhypertensionthroughnmrspectroscopy |
_version_ |
1724373855872483328 |