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Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface
Docking of over 160 aminothiourea derivatives at the SARS-CoV-2 S-protein–human ACE2 receptor interface, whose structure became available recently, has been evaluated for its complex stabilizing potency and subsequently subjected to quantitative structure–activity relationship (QSAR) analysis. The s...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656307/ https://www.ncbi.nlm.nih.gov/pubmed/33053830 http://dx.doi.org/10.3390/molecules25204645 |
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author | Płonka, Wojciech Paneth, Agata Paneth, Piotr |
author_facet | Płonka, Wojciech Paneth, Agata Paneth, Piotr |
author_sort | Płonka, Wojciech |
collection | PubMed |
description | Docking of over 160 aminothiourea derivatives at the SARS-CoV-2 S-protein–human ACE2 receptor interface, whose structure became available recently, has been evaluated for its complex stabilizing potency and subsequently subjected to quantitative structure–activity relationship (QSAR) analysis. The structural variety of the studied compounds, that include 3 different forms of the N–N–C(S)–N skeleton and combinations of 13 different substituents alongside the extensive length of the interface, resulted in the failure of the QSAR analysis, since different molecules were binding to different parts of the interface. Subsequently, absorption, distribution, metabolism, and excretion (ADME) analysis on all studied compounds, followed by a toxicity analysis using statistical models for selected compounds, was carried out to evaluate their potential use as lead compounds for drug design. Combined, these studies highlighted two molecules among the studied compounds, i.e., 5-(pyrrol-2-yl)-2-(2-methoxyphenylamino)-1,3,4-thiadiazole and 1-(cyclopentanoyl)-4-(3-iodophenyl)-thiosemicarbazide, as the best candidates for the development of future drugs. |
format | Online Article Text |
id | pubmed-7656307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76563072020-11-12 Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface Płonka, Wojciech Paneth, Agata Paneth, Piotr Molecules Article Docking of over 160 aminothiourea derivatives at the SARS-CoV-2 S-protein–human ACE2 receptor interface, whose structure became available recently, has been evaluated for its complex stabilizing potency and subsequently subjected to quantitative structure–activity relationship (QSAR) analysis. The structural variety of the studied compounds, that include 3 different forms of the N–N–C(S)–N skeleton and combinations of 13 different substituents alongside the extensive length of the interface, resulted in the failure of the QSAR analysis, since different molecules were binding to different parts of the interface. Subsequently, absorption, distribution, metabolism, and excretion (ADME) analysis on all studied compounds, followed by a toxicity analysis using statistical models for selected compounds, was carried out to evaluate their potential use as lead compounds for drug design. Combined, these studies highlighted two molecules among the studied compounds, i.e., 5-(pyrrol-2-yl)-2-(2-methoxyphenylamino)-1,3,4-thiadiazole and 1-(cyclopentanoyl)-4-(3-iodophenyl)-thiosemicarbazide, as the best candidates for the development of future drugs. MDPI 2020-10-12 /pmc/articles/PMC7656307/ /pubmed/33053830 http://dx.doi.org/10.3390/molecules25204645 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Płonka, Wojciech Paneth, Agata Paneth, Piotr Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface |
title | Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface |
title_full | Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface |
title_fullStr | Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface |
title_full_unstemmed | Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface |
title_short | Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface |
title_sort | docking and qsar of aminothioureas at the sars-cov-2 s-protein–human ace2 receptor interface |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656307/ https://www.ncbi.nlm.nih.gov/pubmed/33053830 http://dx.doi.org/10.3390/molecules25204645 |
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