6533b7dbfe1ef96bd12714c0
RESEARCH PRODUCT
Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line
Manuela LabbozzettaMarilia BarrecaVirginia SpanòMaria Valeria RaimondiPaola PomaMonica NotarbartoloPaola BarrajaAlessandra Montalbanosubject
Leukemia Myeloid AcuteDrug Resistance Neoplasmantimitotic agents [12]oxazolo[54‐e]isoindoles multidrug resistanceDrug DiscoverySettore BIO/14 - FarmacologiaHumansAntineoplastic AgentsIsoindolesSettore CHIM/08 - Chimica FarmaceuticaDrug Resistance MultipleCell Linedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-06-24 |