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

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 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.

Novel 7-Chloro-4-aminoquinoline-benzimidazole Hybrids as Inhibitors of Cancer Cells Growth: Synthesis, Antiproliferative Activity, in Silico ADME Predictions, and Docking

“…Cancer is a leading disease worldwide, and the projections indicate that the global incidence of cancer will continue to rise [ 1 , 2 ]. The conventional anti-cancer agents are losing their efficiency [ 3 ], highlighting the need to introduce new anti-cancer entities [ 4 , 5 , 6 ]. One strategy to address the issues with existing chemotherapeutics is molecular hybridization: a strategy that generates more efficient therapeutics by combining two (or more) pharmacophores or two (or more) entire drugs in a single hybrid molecule that addresses one or multiple targets [ 7 , 8 , 9 ].…”

A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia

“…Several RTKs are mutated or overexpressed in human cancers and are likely to be involved in constitutive activation of survival and proliferative signaling, and thereby, disease progression [ 2 ]. Therefore, inhibition of RTKs has become an attractive approach for the treatment of several cancers [ 3 , 4 ]. However, the development of primary and secondary resistance to RTK-targeted therapies limits its clinical application [ 5 , 6 ].…”

New tricyclic systems as photosensitizers towards triple negative breast cancer cells

“…Small molecules show several advantages as they typically possess fast distribution throughout the body, rapid clearance, and target accumulation at the tumour site. During our studies aiming at the development of new bioactive heterocyclic compounds (Spanò et al 2021a , b ; Barreca et al 2022b ; Cilibrasi et al 2022 ; Labbozzetta et al 2022 ), we explored several classes of PSs, and some of them showed high potency, with outstanding selectivity index versus tumour cells inducing mitochondrial apoptotic death (Spanò et al 2017 ). We recently reported our studies on two classes of small heterocyclic compounds, namely pyrimido[5,4- g ]indolizines 1 and pyrimido[4,5- c ]pyrrolo[1,2- a ]azepines 2 (Fig.…”

“…Small molecules show several advantages as they typically possess fast distribution throughout the body, rapid clearance, and target accumulation at the tumour site. During our studies aiming at the development of new bioactive heterocyclic compounds (Spanò et al 2021a, b;Barreca et al 2022b;Cilibrasi et al 2022;Labbozzetta et al 2022), we explored several classes of PSs, and some of them showed high potency, with outstanding selectivity index versus Abstract Nineteen pyrrolo [1,2-h][1,7]naphthyridinones and pyrido [2,3-c]pyrrolo [1,2-a]azepinones were synthesized as new tricyclic systems in which the pyridine ring is annelated to the 6,7-dihydroindolizin-8(5H)-one and 5,6,7,8-tetrahydro-9H-pyrrole[1,2-a]azepine-9-one moieties to obtain potential photosensitizing agents. They were tested for their photoantiproliferative activity on a triple-negative breast cancer cell line, MDA-MB-231, in the dark and under UVA light (2.0 J/cm 2 ).…”