Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity

A new series of ( ±)-(3-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-yl)(phenyl)methanones were efficiently synthesized starting from 4-amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol 1, acetyl acetone 2, various aromatic and heterocyclic aldehydes 3...

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Autores principales: Jilloju, Parameshwara Chary, Persoons, Leentje, Kurapati, Sathish Kumar, Schols, Dominique, De Jonghe, Steven, Daelemans, Dirk, Vedula, Rajeswar Rao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223195/
https://www.ncbi.nlm.nih.gov/pubmed/34165689
http://dx.doi.org/10.1007/s11030-021-10258-8
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author Jilloju, Parameshwara Chary
Persoons, Leentje
Kurapati, Sathish Kumar
Schols, Dominique
De Jonghe, Steven
Daelemans, Dirk
Vedula, Rajeswar Rao
author_facet Jilloju, Parameshwara Chary
Persoons, Leentje
Kurapati, Sathish Kumar
Schols, Dominique
De Jonghe, Steven
Daelemans, Dirk
Vedula, Rajeswar Rao
author_sort Jilloju, Parameshwara Chary
collection PubMed
description A new series of ( ±)-(3-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-yl)(phenyl)methanones were efficiently synthesized starting from 4-amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol 1, acetyl acetone 2, various aromatic and heterocyclic aldehydes 3 and phenacyl bromides 4. All the newly synthesized compounds were tested for their antiviral and antitumoral activity. It was shown that subtle structural variations on the phenyl moiety allowed to tune biological properties toward antiviral or antitumoral activity. Mode-of-action studies revealed that the antitumoral activity was due to inhibition of tubulin polymerization. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-021-10258-8.
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spelling pubmed-82231952021-06-25 Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity Jilloju, Parameshwara Chary Persoons, Leentje Kurapati, Sathish Kumar Schols, Dominique De Jonghe, Steven Daelemans, Dirk Vedula, Rajeswar Rao Mol Divers Original Article A new series of ( ±)-(3-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-yl)(phenyl)methanones were efficiently synthesized starting from 4-amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol 1, acetyl acetone 2, various aromatic and heterocyclic aldehydes 3 and phenacyl bromides 4. All the newly synthesized compounds were tested for their antiviral and antitumoral activity. It was shown that subtle structural variations on the phenyl moiety allowed to tune biological properties toward antiviral or antitumoral activity. Mode-of-action studies revealed that the antitumoral activity was due to inhibition of tubulin polymerization. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-021-10258-8. Springer International Publishing 2021-06-24 2022 /pmc/articles/PMC8223195/ /pubmed/34165689 http://dx.doi.org/10.1007/s11030-021-10258-8 Text en © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Jilloju, Parameshwara Chary
Persoons, Leentje
Kurapati, Sathish Kumar
Schols, Dominique
De Jonghe, Steven
Daelemans, Dirk
Vedula, Rajeswar Rao
Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity
title Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity
title_full Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity
title_fullStr Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity
title_full_unstemmed Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity
title_short Discovery of (  ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity
title_sort discovery of (  ±)-3-(1 h -pyrazol-1-yl)-6,7-dihydro-5 h -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223195/
https://www.ncbi.nlm.nih.gov/pubmed/34165689
http://dx.doi.org/10.1007/s11030-021-10258-8
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