Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator

Salehi, Samie; Saljooghi, Amir SHokooh; Shiri, Ali

doi:10.1016/j.ejphar.2016.04.026

Cited by 15 publications

(13 citation statements)

References 42 publications

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“…The deferasirox‐based ligand LH 2 appeared particularly cytotoxic, with IC 50 values down to the sub‐micromolar level, and was more than six times more active than that of deferasirox (IC 50 =(4.4±1.2) μ m ) on the MDA‐MB‐231 cell line . All tested complexes appeared more toxic than that of cisplatin toward the triple‐negative breast cancer cell line MDA‐MB‐231 and, with the exception of 2 d , all complexes were also more toxic than that of cisplatin toward MCF‐7 cell line.…”

Section: Resultsmentioning

confidence: 99%

A Bis‐Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents

Bertrand

Botuha

Forté

et al. 2020

Chemistry A European J

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The two independent O _ N _ Oa nd N _ Nc oordination sites of an ewly synthesized bis[2-(hydroxyphenyl)-1,2,4-triazole] platform have been exploited to prepare fourm onometallic neutral (O _ N _ O)Pt II complexes carryingD MSO, pyridine, triphenylphosphine, or N-heterocyclic carbene as the fourth ligand.T hen, the second N _ Nc oordination site was used to introduce an IR-active rhenium tricarbonyl entity,a ffording the four correspondingh eterobimetallic neutral Pt II / Re I complexes,a sw ell as ac ationic Pt II /Re I derivative.X-ray crystallographic studiess howed that distortiono ft he organic platform occurred to accommodate the coordination geometry of both metal centers. No ligand exchange or transchelation occurred upon incubation of the Pt II complexes in aqueouse nvironment or in the presence of Fe III ,r espectively. The antiproliferativea ctivity of the ligand and complexes was first screened on the triple-negative breast cancerc ell line MDA-MB-231. Then, the IC 50 values of the most active candidates were determined on aw ider panel of human cancerc ells (MDA-MB-231, MCF-7, and A2780), as well as on anontumorigenic cell line (MCF-10A). Low micromolar activities were reached for the complexes carrying aD MSO ligand, making them the first examples of highly active, but hydrolytically stable, Pt II complexes. Finally,t he characteristic mid-IRs ignature of the {Re(CO) 3 }f ragment in the Pt/Re heterobimetallic complexes wasu sed to quantify their uptake in breast cancer cells.

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Section: Resultsmentioning

confidence: 99%

A Bis‐Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents

Bertrand

Botuha

Forté

et al. 2020

Chemistry A European J

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“…The synthetic route employed (Scheme 1) followed that of reported syntheses of this structural class and the commercial deferasirox process. [52][53][54][55][56] This efficient two-step protocol started with condensation of appropriately substituted salicylamides 4 The substituted derivatives 3b-f were tested in the in vitro assays against JMJD2A (Table 1) and found to be active in a concentration range similar to 3a. In order to investigate the relevance of the tridentate iron-binding motif composed of triazole-N and two phenol-O atoms in deferasirox 3a for potent inhibition, we designed two structural analogues 12a and 12b…”

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confidence: 99%

“…Thus, using a low concentration of Fe 2+ in these inhibition assays, 1 and 3a were moderately potent PHD2 inhibitors (2.4 ± 0.2 μM and 2.4 ± 0.2 μM, respectively), but at higher Indeed, there is already some evidence for a beneficial in vivo effect when cancer cells or patients have been treated with 3a. 56,[61][62][63][64][65] Treatment with 1 or 3a has been reported to inhibit proliferation of esophageal cancer cells in cell culture and a mouse xenograft model and increased susceptibility to standard chemotherapy. The mechanism of action, however, was elusive.…”

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confidence: 99%

The Clinically Used Iron Chelator Deferasirox Is an Inhibitor of Epigenetic JumonjiC Domain-Containing Histone Demethylases

et al. 2019

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Supporting Information available: This material is available free of charge via the internet. It includes further enzyme inhibition data (MS), enzyme kinetic analyses, detailed EPR spectroscopic analyses, NMR binding experiments of control compounds, docking structures, as well as further analyses of the cellular effects of deferasirox (cell proliferation, western blots, immunostaining). Additional experimental methods are presented. AUTHOR INFORMATION

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“…Nowadays, different chelators are being used for this purpose. Currently, combination therapy with L1 and DFO, which are highly selective for iron (III) under biological conditions (pFe 3+ = 26.6), is reported to be the most effective treatment for many patients ( 19 , 20 ). Undoubtedly, DFX, possessing a higher pFe 3+ value than L1 does, behaves in a similar manner.…”

Section: Discussionmentioning

confidence: 99%

Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy

et al. 2017

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Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days. It was hypothesized that the two chelators might be more efficient as a combined therapy than as monotherapies in removing thallium (III) from the rats’ organs. The chelators were administered orally as either single or combined therapies for a period of 14 days. Serum and tissue thallium (III) and iron concentrations were determined by flame atomic absorption spectroscopy. Serum and tissue thallium (III) levels were significantly reduced by combined therapy with DFX and L1. Additionally, iron concentrations returned to normal levels and symptoms of toxicity decreased.

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Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator

Cited by 15 publications

References 42 publications

A Bis‐Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents

A Bis‐Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents

The Clinically Used Iron Chelator Deferasirox Is an Inhibitor of Epigenetic JumonjiC Domain-Containing Histone Demethylases

Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy

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