Gold(I) complexes with thiosemicarbazones: Cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Lessa, Josane A.; Guerra, Juliana C.; Miranda, Luana F. de; Romeiro, Carla F.D.; Silva, Jéferson G. Da; Mendes, Isolda C.; Speziali, Nivaldo L.; Souza-Fagundes, Elaine M.; Beraldo, Heloísa

doi:10.1016/j.jinorgbio.2011.09.008

Cited by 62 publications

(28 citation statements)

References 38 publications

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“…Following this reasoning, the [Pd(TSC 3 ) 2 ] ( 8 ) complex, with the 4-phenyl-1-(3′-hydroxy-benzaldehyde) thiosemicarbazone ligand, was also more active than the palladium(II) bis-chelate complex of 3′-cyano-benzaldehyde thiosemicarbazone (IC 50 = 0.45–3.53 μ M) against all human tumor cell lines tested [27]. In addition, complex ( 8 ) was found to be about thirteen times more cytotoxic than the gold(I) complex from 4-methyl-1-(2′-acetylpyridine) thiosemicarbazone ligand (IC 50 = 1.65 μ M) against the (MCF-7) human breast adenocarcinoma tumor cell line [49]. With respect to the cytotoxic activity shown by the ruthenium(II) complex of the [Ru(Phen) 2 (L)]Cl 2 type, with L being a 3-methoxy, or 4-hydroxy-benzaldehyde thiosemicarbazone ligand (IC 50 = 3.60 μ M) assayed on the (CEM) human leukemia cell line [24], complex ( 8 ) presented higher cytotoxicity at low micromolar concentrations (IC 50 = 0.02 μ M) tested in vitro against the (K562) chronic myelogenous leukemia cell line.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

Hernández

Paz

Carrasco

et al. 2013

Bioinorganic Chemistry and Applications

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The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.).

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Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

Hernández

Paz

Carrasco

et al. 2013

Bioinorganic Chemistry and Applications

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“…Studies have shown that TrxR is a key molecule involved in the intracellular regulation of mitochondrial dysfunction and oxidative stress signaling . Most gold complexes have been reported to cause computable mitochondrial dysfunction and give rise to cancer cell death . We used the JC‐1 kit to test the mitochondrial membrane potential (MMP) on treatment of 4 b (5 μ m , 10 μ m , and 15 μ m ) and OA (100 μ m ).…”

Section: Resultsmentioning

confidence: 99%

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

Bian

Sun

Liu

et al. 2020

Chemistry A European J

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Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to furthero xidative impairment triggered by agentsg enerating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be ap romising anticancer strategy.H erein, it is shown that ag old(I) complex containing an oleanolic acid derivative (4b)i nduces apopto-sis of ovarian cancerA 2780 cells by activatinge ndoplasmic reticulum stress (ERS). It can inhibitT rxR enzymea ctivity to elevateR OS, mediate ERS and mitochondriald ysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably,t his complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues.[a] Dr.[ + + ] These authors contributed equally to this work.[**] ERS:e ndoplasmic reticulums tress, ROS:r eactive oxygen species, TrxR:t hioredoxin reductase.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

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“…Beraldo and co‐workers replaced the thiol‐carbohydrate moiety with S‐donor ligands and prepared several gold (I) complexes‐bearing a 2‐acetylpyridine thiosemicarbazone ( 5–7, Figure A) scaffold and tested their cytotoxicity against a panel of solid and leukemia cancer cells (Table ). Among these compounds, complex 5 strongly inhibited the activity of rat liver TrxR with IC 50 value of 2.48 μM, suggesting TrxR as a possible target for the cytotoxicity of the complex . In addition, they also reported that the gold (III)‐containing complex ( 8 ) possesses highly potency against THP‐1, HL‐60, MCF‐7, and MDA‐MB 231 cancer cell lines (Table ).…”

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 97%

“…Due to the high affinity of sulfur/selenium with noble metals, these inhibitors, in general, are highly potent with IC 50 values in a nanomolar range (see the data listed in Table ). The ligands of metal complexes also play a significant role in determining the inhibition potency as they may contribute to the stability as well as cell membrane permeability of the complexes, and the weak interactions with TrxR …”

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Zhang

et al. 2018

Medicinal Research Reviews

131

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Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C-terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years. Herein, we briefly discussed the relevance of targeting TrxRs inhibition for cancer treatment, and presented the small molecule inhibitors of mammalian TrxRs published in the nonpatent literatures from 2011 to 2016. The mechanisms of inhibition by different classes of molecules were summarized, and some inhibitors with promising anticancer activity were further discussed. We expect this work would be a comprehensive reference in the medicinal chemistry, and have a broad audience across multiple disciplines.

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Gold(I) complexes with thiosemicarbazones: Cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Cited by 62 publications

References 38 publications

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

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