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Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units
Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmace...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780263/ https://www.ncbi.nlm.nih.gov/pubmed/35056929 http://dx.doi.org/10.3390/pharmaceutics14010033 |
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author | Rodríguez, Diego F. Durán-Osorio, Francisca Duarte, Yorley Olivares, Pedro Moglie, Yanina Dua, Kamal Zacconi, Flavia C. |
author_facet | Rodríguez, Diego F. Durán-Osorio, Francisca Duarte, Yorley Olivares, Pedro Moglie, Yanina Dua, Kamal Zacconi, Flavia C. |
author_sort | Rodríguez, Diego F. |
collection | PubMed |
description | Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC(50)-values as low as 17.2 μM and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential. |
format | Online Article Text |
id | pubmed-8780263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87802632022-01-22 Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units Rodríguez, Diego F. Durán-Osorio, Francisca Duarte, Yorley Olivares, Pedro Moglie, Yanina Dua, Kamal Zacconi, Flavia C. Pharmaceutics Article Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC(50)-values as low as 17.2 μM and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential. MDPI 2021-12-24 /pmc/articles/PMC8780263/ /pubmed/35056929 http://dx.doi.org/10.3390/pharmaceutics14010033 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rodríguez, Diego F. Durán-Osorio, Francisca Duarte, Yorley Olivares, Pedro Moglie, Yanina Dua, Kamal Zacconi, Flavia C. Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units |
title | Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units |
title_full | Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units |
title_fullStr | Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units |
title_full_unstemmed | Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units |
title_short | Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units |
title_sort | green by design: convergent synthesis, computational analyses, and activity evaluation of new fxa inhibitors bearing peptide triazole linking units |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780263/ https://www.ncbi.nlm.nih.gov/pubmed/35056929 http://dx.doi.org/10.3390/pharmaceutics14010033 |
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