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(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia
The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) gr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Beilstein-Institut
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450943/ https://www.ncbi.nlm.nih.gov/pubmed/34621389 http://dx.doi.org/10.3762/bjoc.17.144 |
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author | Pimentel, Luiz Claudio Ferreira Hoelz, Lucas Villas Boas Canzian, Henayle Fernandes Branco, Frederico Silva Castelo de Oliveira, Andressa Paula Campos, Vinicius Rangel Júnior, Floriano Paes Silva Dantas, Rafael Ferreira Resende, Jackson Antônio Lamounier Camargos Cunha, Anna Claudia Boechat, Nubia Bastos, Mônica Macedo |
author_facet | Pimentel, Luiz Claudio Ferreira Hoelz, Lucas Villas Boas Canzian, Henayle Fernandes Branco, Frederico Silva Castelo de Oliveira, Andressa Paula Campos, Vinicius Rangel Júnior, Floriano Paes Silva Dantas, Rafael Ferreira Resende, Jackson Antônio Lamounier Camargos Cunha, Anna Claudia Boechat, Nubia Bastos, Mônica Macedo |
author_sort | Pimentel, Luiz Claudio Ferreira |
collection | PubMed |
description | The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results, with IC(50) values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1 in the docking studies. |
format | Online Article Text |
id | pubmed-8450943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-84509432021-10-06 (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia Pimentel, Luiz Claudio Ferreira Hoelz, Lucas Villas Boas Canzian, Henayle Fernandes Branco, Frederico Silva Castelo de Oliveira, Andressa Paula Campos, Vinicius Rangel Júnior, Floriano Paes Silva Dantas, Rafael Ferreira Resende, Jackson Antônio Lamounier Camargos Cunha, Anna Claudia Boechat, Nubia Bastos, Mônica Macedo Beilstein J Org Chem Full Research Paper The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results, with IC(50) values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1 in the docking studies. Beilstein-Institut 2021-09-01 /pmc/articles/PMC8450943/ /pubmed/34621389 http://dx.doi.org/10.3762/bjoc.17.144 Text en Copyright © 2021, Pimentel et al. https://creativecommons.org/licenses/by/4.0/https://www.beilstein-journals.org/bjoc/terms/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ). Please note that the reuse, redistribution and reproduction in particular requires that the author(s) and source are credited and that individual graphics may be subject to special legal provisions. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms/terms) |
spellingShingle | Full Research Paper Pimentel, Luiz Claudio Ferreira Hoelz, Lucas Villas Boas Canzian, Henayle Fernandes Branco, Frederico Silva Castelo de Oliveira, Andressa Paula Campos, Vinicius Rangel Júnior, Floriano Paes Silva Dantas, Rafael Ferreira Resende, Jackson Antônio Lamounier Camargos Cunha, Anna Claudia Boechat, Nubia Bastos, Mônica Macedo (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia |
title | (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia |
title_full | (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia |
title_fullStr | (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia |
title_full_unstemmed | (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia |
title_short | (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia |
title_sort | (phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia |
topic | Full Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450943/ https://www.ncbi.nlm.nih.gov/pubmed/34621389 http://dx.doi.org/10.3762/bjoc.17.144 |
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