Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Shahinshavali, Shaik, Hossain, Kazi Amirul, Kumar, Abbaraju Venkata Durga Nagendra, Reddy, Alugubelli Gopi, Kolli, Deepti, Nakhi, Ali, Rao, Mandava Venkata Basaveswara, Pal, Manojit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2020
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
_version_ 1783574733082591232
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
work_keys_str_mv AT shahinshavalishaik ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2
AT hossainkaziamirul ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2
AT kumarabbarajuvenkatadurganagendra ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2
AT reddyalugubelligopi ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2
AT kollideepti ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2
AT nakhiali ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2
AT raomandavavenkatabasaveswara ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2
AT palmanojit ultrasoundassistedsynthesisof3alkynylsubstituted2chloroquinoxalinederivativestheirinsilicoassessmentaspotentialligandsfornproteinofsarscov2