α−N−heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its antitumor activity and identification of anticancer mechanism

Gou, Yanzi; Wang, Jun; Chen, Shifang; Zhang, Zhan; Zhang, Yao; Zhang, Wei; Yang, Feng

doi:10.1016/j.ejmech.2016.07.041

Cited by 73 publications

(25 citation statements)

References 70 publications

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“…This feature enables these compounds to be used in the treatment of cancer diseases. There are also substances with ortho -hydroxyaldiminecarbazyne structure which coordinate the iron atoms [6,7]. Their presence in the organism regulates the amount of iron in cells, thus preventing the formation of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Some Brief Notes on Theoretical and Experimental Investigations of Intramolecular Hydrogen Bonding

et al. 2016

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Abstract:A review of selected literature data related to intramolecular hydrogen bonding in ortho-hydroxyaryl Schiff bases, ortho-hydroxyaryl ketones, ortho-hydroxyaryl amides, proton sponges and ortho-hydroxyaryl Mannich bases is presented. The paper reports on the application of experimental spectroscopic measurements (IR and NMR) and quantum-mechanical calculations for investigations of the proton transfer processes, the potential energy curves, tautomeric equilibrium, aromaticity etc. Finally, the equilibrium between the intra-and inter-molecular hydrogen bonds in amides is discussed.

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Section: Introductionmentioning

confidence: 99%

Some Brief Notes on Theoretical and Experimental Investigations of Intramolecular Hydrogen Bonding

et al. 2016

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“…The Fe(III)/Fe(II) redox potentials of the complexes (0.085–0.238 V vs. NHE) fall in the wide range accessible by cellular oxidants and reductants. Also, they vary in the order 1 (0.143) < 2 (0.237) > 3 (0.109) > 4 (0.085 V), illustrating the influence of the σ‐donating and π‐accepting properties of ligand donors and variation in the inductive effect of substituents on ligand backbone on the Fe(III)/Fe(II) redox couple . Thus, the replacement of the methyl group in 1 by the electron‐withdrawing phenyl group to obtain 2 facilitates reduction of iron(III), leading to raise the Fe(III)/Fe(II) redox potential significantly (94 mV).…”

Section: Resultsmentioning

confidence: 98%

Iron(III) bis‐complexes of Schiff bases of S‐methyldithiocarbazates: Synthesis, structure, spectral and redox properties and cytotoxicity

Sohtun

Khamrang

Kannan

et al. 2020

Applied Organom Chemis

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A series of iron(III) bis‐complexes of the type [FeL2]X 1‐4, X = OH− (1), Cl¯ (3), and FeCl4¯ (2, 4), where LH is a tridentate (N,N,S) ligands such as N′‐(1‐pyridin‐2‐ylethylidene)‐hydrazinecarbodithioic acid methyl ester (HL1), N′‐(phenylpyridin‐2‐ylmethylene)‐hydrazinecarbodithioic acid methyl ester (HL2), N′‐quinolin‐2‐ylmethylene‐hydrazinecarbodithioic acid methyl ester (HL3), or N′‐(1‐methyl‐1H‐imidazol‐2‐yl‐methylene)hydrazinecarbodithioic acid methyl ester (HL4) has been isolated in moderate to good yields and completely characterized by elemental analyses, conductivity studies, and infrared and UV‐visible spectral measurements. The single crystal X‐ray structures of 1, 2 and 4 revealed that two deprotonated tridentate (NNS) ligands are meridionally coordinated to constitute a distorted octahedral coordination geometry around iron(III). In acetonitrile solution, all the complexes show quasi‐reversible Fe(III)/Fe(II) redox behavior. The in vitro cytotoxicity of the ligands HL1–HL4 (IC50: HL1, 64.5; HL2, 51.0; HL3, 124.0; HL4, 45.0 μM at 24 h) and complexes 1–4 (IC50: 1, 84.5; 2, 40.0; 3, 168.5; 4, 50.5 μM at 24 h) towards A549 lung cancer cell lines are similar to cisplatin (69.0 μM), revealing that free ligands cause cancer cell death with potency higher than the corresponding iron(III) complexes. Also, both the ligands and the complexes cause cell death mainly through apoptotic mode, as revealed by the observation of a higher percentage of apoptotic cells in acridine orange (AO)/ ethidium bromide (EB), and Annexin V‐Cy3 stained cancer cells.

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“…Recently, researchers have investigated widely about metal-based complexes for cancer therapy, with various types of metallic antitumor candidates being developed for decades, such as gold (Au) and Au-NHCs complexes (Fung et al, 2017; Porchia et al, 2018; Williams et al, 2018), ruthenium (Ru) complexes (Tan et al, 2010), iridium (Ir) complexes (Cao et al, 2013), iron (Fe) complexes (Gou et al, 2016), etc. For instance, Che et al found that Au (III) complexes containing special ligand could act as smart fluorescent probes and anticancer agents (Zou et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…To date, Fe (II) polypyridyl complexes have been considered as promising antiproliferative agents against cancer cells, including ferrocenyl-containing complexes (Zhao et al, 2012) and Fe (II/III) polypyridyl complexes (Gou et al, 2016; Xie et al, 2017). Herein, based on previous study, we studied the anticancer activities of Fe(PIP) 3 SO 4 (Chen et al, 2015) against glioma U87 cells, including regulating the expression levels of p53 and 4E-BP1, triggering cell apoptosis and cycle arrest to inhibit cell proliferation, downregulating cellular reactive oxygen species (ROS) levels and TrxR activity, and penetrating across BBB, which was accompanied with negligible toxicity on normal tissues in vivo .…”

Section: Introductionmentioning

confidence: 99%

Iron (II) Polypyridyl Complexes as Antiglioblastoma Agents to Overcome the Blood-Brain Barrier and Inhibit Cell Proliferation by Regulating p53 and 4E-BP1 Pathways

Zhu

Dai

et al. 2019

Front. Pharmacol.

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Background and Purpose: It is urgently required to develop promising candidates to permeate across blood-brain barrier (BBB) efficiently with simultaneous disrupting vasculogenic mimicry capability of gliomas. Previously, a series of iron (II) complexes were synthesized through a modified method. Hence, the aim of this study was to evaluate anticancer activity of Fe(PIP)3SO4 against glioma cancer cells. Methods: Cytotoxic effects were determined via MTT assay, and IC50 values were utilized to evaluate the cytotoxicity. Cellular uptake of Fe(PIP)3SO4 between U87 and HEB cells was conducted by subtracting content of the complex remaining in the cell culture supernatants. Propidium Iodide (PI)-flow cytometric analysis was used to analyze cell cycle proportion of U87 cells treated with Fe(PIP)3SO4. The reactive oxygen species levels induced by Fe(PIP)3SO4 were measured by 2'-deoxycoformycin (DCF) probe; ABTS assay was utilized to examine the radical scavenge capacity of Fe(PIP)3SO4. To study the bind efficiency to thioredoxin reductase (TrxR), Fe(PIP)3SO4 was introduced into solution containing TrxR. To verify if Fe(PIP)3SO4 could penetrate BBB, HBMEC/U87 coculture as BBB model was established, and penetrating capability of Fe(PIP)3SO4 was tested. In vitro U87 tumor spheroids were formed to test the permeating ability of Fe(PIP)3SO4. Acute toxicity and biodistribution of Fe(PIP)3SO4 were tested on mice for 72 h. Protein profiles associated with U87 cells treated with Fe(PIP)3SO4 were determined by Western blotting analysis. Results: Results showed that Fe(PIP)3SO4 could suppress cell proliferation by inducing G2/M phase cycle retardation and apoptotic pathways, which was related with expression of p53 and initiation factor 4E binding protein 1. In addition, Fe complex could suppress cell proliferation by downregulating reactive oxygen species levels via scavenging free radicals and interaction with TrxR. Furthermore, Fe(PIP)3SO4 could permeate across BBB and simultaneously inhibited the vasculogenic mimicry-channel of U87 cells, suggesting favorable antiglioblastoma efficacy. Acute toxicity manifested lower degree of the complex compared with cisplatin and temozolomide. Conclusion: Fe(PIP)3SO4 exhibited favorable anticancer activity against glioma cells associated with p53 and 4E binding protein 1, accompanied with negligible toxic effects on normal tissues. Herein, Fe(PIP)3SO4 could be developed as a promising metal-based chemotherapeutic agent to overcome BBB and antagonize glioblastomas.

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α−N−heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its antitumor activity and identification of anticancer mechanism

Cited by 73 publications

References 70 publications

Some Brief Notes on Theoretical and Experimental Investigations of Intramolecular Hydrogen Bonding

Some Brief Notes on Theoretical and Experimental Investigations of Intramolecular Hydrogen Bonding

Iron(III) bis‐complexes of Schiff bases of S‐methyldithiocarbazates: Synthesis, structure, spectral and redox properties and cytotoxicity

Iron (II) Polypyridyl Complexes as Antiglioblastoma Agents to Overcome the Blood-Brain Barrier and Inhibit Cell Proliferation by Regulating p53 and 4E-BP1 Pathways

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