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Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line

A series of [1,2]oxazolo[5,4‐e]isoindole derivatives was evaluated against HL‐60 cell line and its multidrug resistance (MDR) variant, HL‐60R, resistant to doxorubicin and to other P‐gp substrates by overexpressing the efflux pump. They displayed antiproliferative activities, with IC(50) values rang...

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Autores principales: Labbozzetta, Manuela, Barreca, Marilia, Spanò, Virginia, Raimondi, Maria Valeria, Poma, Paola, Notarbartolo, Monica, Barraja, Paola, Montalbano, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540667/
https://www.ncbi.nlm.nih.gov/pubmed/35749723
http://dx.doi.org/10.1002/ddr.21962
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author Labbozzetta, Manuela
Barreca, Marilia
Spanò, Virginia
Raimondi, Maria Valeria
Poma, Paola
Notarbartolo, Monica
Barraja, Paola
Montalbano, Alessandra
author_facet Labbozzetta, Manuela
Barreca, Marilia
Spanò, Virginia
Raimondi, Maria Valeria
Poma, Paola
Notarbartolo, Monica
Barraja, Paola
Montalbano, Alessandra
author_sort Labbozzetta, Manuela
collection PubMed
description A series of [1,2]oxazolo[5,4‐e]isoindole derivatives was evaluated against HL‐60 cell line and its multidrug resistance (MDR) variant, HL‐60R, resistant to doxorubicin and to other P‐gp substrates by overexpressing the efflux pump. They displayed antiproliferative activities, with IC(50) values ranging from 0.02 to 5.5 µM. In particular, the newly synthesized compound 4k produced synergistic effects in terms of cell growth inhibition and cell death induction either in combination with a Vinca alkaloid, Vinblastine, and a Taxane, Paclitaxel in HL‐60R cells. The study of the mechanism of action indicated that all compounds showed antimitotic activity through inhibition of tubulin polymerization. Thus, [1,2]oxazoles could represent a valuable tool to overcome MDR mechanism, confirming the potential use of this class of compounds.
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spelling pubmed-95406672022-10-14 Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line Labbozzetta, Manuela Barreca, Marilia Spanò, Virginia Raimondi, Maria Valeria Poma, Paola Notarbartolo, Monica Barraja, Paola Montalbano, Alessandra Drug Dev Res Research Articles A series of [1,2]oxazolo[5,4‐e]isoindole derivatives was evaluated against HL‐60 cell line and its multidrug resistance (MDR) variant, HL‐60R, resistant to doxorubicin and to other P‐gp substrates by overexpressing the efflux pump. They displayed antiproliferative activities, with IC(50) values ranging from 0.02 to 5.5 µM. In particular, the newly synthesized compound 4k produced synergistic effects in terms of cell growth inhibition and cell death induction either in combination with a Vinca alkaloid, Vinblastine, and a Taxane, Paclitaxel in HL‐60R cells. The study of the mechanism of action indicated that all compounds showed antimitotic activity through inhibition of tubulin polymerization. Thus, [1,2]oxazoles could represent a valuable tool to overcome MDR mechanism, confirming the potential use of this class of compounds. John Wiley and Sons Inc. 2022-06-24 2022-09 /pmc/articles/PMC9540667/ /pubmed/35749723 http://dx.doi.org/10.1002/ddr.21962 Text en © 2022 The Authors. Drug Development Research published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Labbozzetta, Manuela
Barreca, Marilia
Spanò, Virginia
Raimondi, Maria Valeria
Poma, Paola
Notarbartolo, Monica
Barraja, Paola
Montalbano, Alessandra
Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
title Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
title_full Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
title_fullStr Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
title_full_unstemmed Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
title_short Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
title_sort novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540667/
https://www.ncbi.nlm.nih.gov/pubmed/35749723
http://dx.doi.org/10.1002/ddr.21962
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