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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/20/4645 |
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| author | Wojciech Płonka Agata Paneth Piotr Paneth |
| author_facet | Wojciech Płonka Agata Paneth Piotr Paneth |
| author_sort | Wojciech Płonka |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T15:41:47Z |
| format | Article |
| id | doaj.art-c283ed92ffca4641bb7e747caa67103c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:41:47Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c283ed92ffca4641bb7e747caa67103c2023-11-20T16:46:03ZengMDPI AGMolecules1420-30492020-10-012520464510.3390/molecules25204645Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor InterfaceWojciech Płonka0Agata Paneth1Piotr Paneth2Center for Bioinformatics (ZBH), Universität Hamburg, 20146 Hamburg, GermanyDepartment of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, PolandInstitute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Lodz, PolandDocking 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.https://www.mdpi.com/1420-3049/25/20/4645SARS-CoV-2aminothioureasdockingQSARADMET |
| spellingShingle | Wojciech Płonka Agata Paneth Piotr Paneth Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface Molecules SARS-CoV-2 aminothioureas docking QSAR ADMET |
| 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 | SARS-CoV-2 aminothioureas docking QSAR ADMET |
| url | https://www.mdpi.com/1420-3049/25/20/4645 |
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