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 IC50 values ranging from 0.02 to 5.5μM. 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.

Manuela Labbozzetta, Marilia Barreca, Virginia Spano', Maria Valeria Raimondi, Paola Poma, Monica Notarbartolo, et al. (2022). Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line. DRUG DEVELOPMENT RESEARCH, 1-11 [10.1002/ddr.21962].

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

Manuela Labbozzetta
Co-primo
Investigation
;
Marilia Barreca
Co-primo
Investigation
;
Virginia Spano'
Secondo
Investigation
;
Maria Valeria Raimondi
Writing – Original Draft Preparation
;
Paola Poma
Writing – Original Draft Preparation
;
Monica Notarbartolo
Supervision
;
Paola Barraja
Penultimo
Supervision
;
Alessandra Montalbano
Ultimo
Supervision
2022

Abstract

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 IC50 values ranging from 0.02 to 5.5μM. 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.
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
https://onlinelibrary.wiley.com/doi/10.1002/ddr.21962
Manuela Labbozzetta, Marilia Barreca, Virginia Spano', Maria Valeria Raimondi, Paola Poma, Monica Notarbartolo, et al. (2022). Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line. DRUG DEVELOPMENT RESEARCH, 1-11 [10.1002/ddr.21962].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/566082
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