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Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2
In view of recent global pandemic the 3-alkynyl substituted 2-chloroquinoxaline framework has been explored as a potential template for the design of molecules targeting COVID-19. Initial in silico studies of representative compounds to assess their binding affinities via docking into the N-terminal...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449981/ https://www.ncbi.nlm.nih.gov/pubmed/32868957 http://dx.doi.org/10.1016/j.tetlet.2020.152336 |
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author | Shahinshavali, Shaik Hossain, Kazi Amirul Kumar, Abbaraju Venkata Durga Nagendra Reddy, Alugubelli Gopi Kolli, Deepti Nakhi, Ali Rao, Mandava Venkata Basaveswara Pal, Manojit |
author_facet | Shahinshavali, Shaik Hossain, Kazi Amirul Kumar, Abbaraju Venkata Durga Nagendra Reddy, Alugubelli Gopi Kolli, Deepti Nakhi, Ali Rao, Mandava Venkata Basaveswara Pal, Manojit |
author_sort | Shahinshavali, Shaik |
collection | PubMed |
description | In view of recent global pandemic the 3-alkynyl substituted 2-chloroquinoxaline framework has been explored as a potential template for the design of molecules targeting COVID-19. Initial in silico studies of representative compounds to assess their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2 prompted further study of these molecules. Thus building of a small library of molecules based on the said template became essential for this purpose. Accordingly, a convenient and environmentally safer method has been developed for the rapid synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives under Cu-catalysis assisted by ultrasound. This simple and straightforward method involved the coupling of 2,3-dichloroquinoxaline with commercially available terminal alkynes in the presence of CuI, PPh(3) and K(2)CO(3) in PEG-400. Further in silico studies revealed some remarkable observations and established a virtual SAR (Structure Activity Relationship) within the series. Three compounds appeared as potential agents for further studies. |
format | Online Article Text |
id | pubmed-7449981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74499812020-08-27 Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2 Shahinshavali, Shaik Hossain, Kazi Amirul Kumar, Abbaraju Venkata Durga Nagendra Reddy, Alugubelli Gopi Kolli, Deepti Nakhi, Ali Rao, Mandava Venkata Basaveswara Pal, Manojit Tetrahedron Lett Article In view of recent global pandemic the 3-alkynyl substituted 2-chloroquinoxaline framework has been explored as a potential template for the design of molecules targeting COVID-19. Initial in silico studies of representative compounds to assess their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2 prompted further study of these molecules. Thus building of a small library of molecules based on the said template became essential for this purpose. Accordingly, a convenient and environmentally safer method has been developed for the rapid synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives under Cu-catalysis assisted by ultrasound. This simple and straightforward method involved the coupling of 2,3-dichloroquinoxaline with commercially available terminal alkynes in the presence of CuI, PPh(3) and K(2)CO(3) in PEG-400. Further in silico studies revealed some remarkable observations and established a virtual SAR (Structure Activity Relationship) within the series. Three compounds appeared as potential agents for further studies. Elsevier Ltd. 2020-10-01 2020-08-27 /pmc/articles/PMC7449981/ /pubmed/32868957 http://dx.doi.org/10.1016/j.tetlet.2020.152336 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Shahinshavali, Shaik Hossain, Kazi Amirul Kumar, Abbaraju Venkata Durga Nagendra Reddy, Alugubelli Gopi Kolli, Deepti Nakhi, Ali Rao, Mandava Venkata Basaveswara Pal, Manojit Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2 |
title | Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2 |
title_full | Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2 |
title_fullStr | Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2 |
title_full_unstemmed | Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2 |
title_short | Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2 |
title_sort | ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: their in silico assessment as potential ligands for n-protein of sars-cov-2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449981/ https://www.ncbi.nlm.nih.gov/pubmed/32868957 http://dx.doi.org/10.1016/j.tetlet.2020.152336 |
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