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Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity

The aqueous dissolution profile of the isomeric synthetic adamantane phenylalkylamine hydrochlorides I and II was probed. These adducts have shown significant antiproliferative/anticancer activity associated with an analgesic profile against neuropathic pain. They are both devoid of toxic effects an...

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Autores principales: Vlachou, Marilena, Foscolos, Angeliki-Sofia, Siamidi, Angeliki, Syriopoulou, Angeliki, Georgiou, Nikitas, Dedeloudi, Aikaterini, Tsiailanis, Antonis D., Tzakos, Andreas G., Mavromoustakos, Thomas, Papanastasiou, Ioannis P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746252/
https://www.ncbi.nlm.nih.gov/pubmed/35011245
http://dx.doi.org/10.3390/molecules27010007
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author Vlachou, Marilena
Foscolos, Angeliki-Sofia
Siamidi, Angeliki
Syriopoulou, Angeliki
Georgiou, Nikitas
Dedeloudi, Aikaterini
Tsiailanis, Antonis D.
Tzakos, Andreas G.
Mavromoustakos, Thomas
Papanastasiou, Ioannis P.
author_facet Vlachou, Marilena
Foscolos, Angeliki-Sofia
Siamidi, Angeliki
Syriopoulou, Angeliki
Georgiou, Nikitas
Dedeloudi, Aikaterini
Tsiailanis, Antonis D.
Tzakos, Andreas G.
Mavromoustakos, Thomas
Papanastasiou, Ioannis P.
author_sort Vlachou, Marilena
collection PubMed
description The aqueous dissolution profile of the isomeric synthetic adamantane phenylalkylamine hydrochlorides I and II was probed. These adducts have shown significant antiproliferative/anticancer activity associated with an analgesic profile against neuropathic pain. They are both devoid of toxic effects and show appreciable enzymatic human plasma stability. The structures of these two compounds have been elucidated using 2D NMR experiments, which were used to study their predominant conformations. Compound II’s scaffold appeared more flexible, as shown by the NOE spatial interactions between the alkyl bridge chain, the aromatic rings, and the adamantane nucleus. Conversely, compound I appeared very rigid, as it did not share significant NOEs between the aforementioned structural segments. MD simulations confirmed the NOE results. The aqueous dissolution profile of both molecules fits well with their minimum energy conformers’ features, which stem from the NOE data; this was nicely demonstrated, especially in the case of compound II.
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spelling pubmed-87462522022-01-11 Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity Vlachou, Marilena Foscolos, Angeliki-Sofia Siamidi, Angeliki Syriopoulou, Angeliki Georgiou, Nikitas Dedeloudi, Aikaterini Tsiailanis, Antonis D. Tzakos, Andreas G. Mavromoustakos, Thomas Papanastasiou, Ioannis P. Molecules Article The aqueous dissolution profile of the isomeric synthetic adamantane phenylalkylamine hydrochlorides I and II was probed. These adducts have shown significant antiproliferative/anticancer activity associated with an analgesic profile against neuropathic pain. They are both devoid of toxic effects and show appreciable enzymatic human plasma stability. The structures of these two compounds have been elucidated using 2D NMR experiments, which were used to study their predominant conformations. Compound II’s scaffold appeared more flexible, as shown by the NOE spatial interactions between the alkyl bridge chain, the aromatic rings, and the adamantane nucleus. Conversely, compound I appeared very rigid, as it did not share significant NOEs between the aforementioned structural segments. MD simulations confirmed the NOE results. The aqueous dissolution profile of both molecules fits well with their minimum energy conformers’ features, which stem from the NOE data; this was nicely demonstrated, especially in the case of compound II. MDPI 2021-12-21 /pmc/articles/PMC8746252/ /pubmed/35011245 http://dx.doi.org/10.3390/molecules27010007 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vlachou, Marilena
Foscolos, Angeliki-Sofia
Siamidi, Angeliki
Syriopoulou, Angeliki
Georgiou, Nikitas
Dedeloudi, Aikaterini
Tsiailanis, Antonis D.
Tzakos, Andreas G.
Mavromoustakos, Thomas
Papanastasiou, Ioannis P.
Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity
title Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity
title_full Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity
title_fullStr Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity
title_full_unstemmed Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity
title_short Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity
title_sort biophysical evaluation and in vitro controlled release of two isomeric adamantane phenylalkylamines with antiproliferative/anticancer and analgesic activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746252/
https://www.ncbi.nlm.nih.gov/pubmed/35011245
http://dx.doi.org/10.3390/molecules27010007
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