In vitro studies of deferasirox derivatives as potential organelle-targeting traceable anti-cancer therapeutics

Abstract

We report here strategic functionalization of the FDA approved chelator deferasirox (1) in an effort to produce organelle-targeting iron chelators with enhanced activity against A549 lung cancer cells. Derivative 8...

Tuning the Solid- and Solution-State Fluorescence of the Iron-Chelator Deferasirox

“…While not a proof, this poor solubility could account for the minimal cytotoxicities seen toward HeLa cells (24-h incubation, see Supporting Information Figure S19). Conversely, this finding leads us to suggest that the good 24-h cytotoxicity seen for a previously reported derivative, Ex-DMED , in human cell lines is due to its relatively greater solubility and cellular permeability with respect to the new derivatives reported in this study. On the other hand, the lack of apparent cytotoxicity led us to consider that the present deferasirox systems might have a role to play in bacterial imaging.…”

“…Because of the pathological role of Fe­(II/III) in several disease states, iron chelators have gained increasing attention for use as potential therapeutics. − In particular, deferasirox, an FDA-approved iron chelator used for the treatment of iron overload, has recently been shown to have anticancer and antimicrobial activity. − However, its nonfluorescent nature means that secondary biological assays are required to determine its cellular uptake, localization, and pharmacokinetic properties . Recent efforts from our group led to the identification of the deferasirox scaffold as an aggregation-induced emission (AIE) platform .…”

Fluorescent Chemosensors for Ion and Molecule Recognition: The Next Chapter

“…This system was based on deferasirox (ExJade) an FDAapproved iron chelator, which is used to treat patients with iron overload. Owing to the pathological role of iron, this system enabled the tracking and detection of disease-based biomarkers while providing inherent therapeutic properties (Steinbrueck et al, 2021;Steinbrueck et al, 2020).…”

2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy

“…One notable system of interest in this context is the FDA-approved iron chelating agent deferasirox (ExJade®, Scheme 1 ) [ 12 , 13 ], which has been shown to exert inhibitory effects towards cancer cells in vitro and in vivo models derived from human liver, lung and pancreatic cells. Promising preliminary success in the treatment of a patient with acute myelogenous leukemia has also been reported [ [14] , [15] , [16] ]. Unfortunately, dose-dependent toxicity and non-targeting issues constitute roadblocks in the clinical development of deferasirox for cancer-related indications.…”