Spectroscopic and electrochemical characterization of gold(I) and gold(III) complexes with glyoxaldehyde bis(thiosemicarbazones): cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Lessa, Josane A.; Ferraz, Karina S.O.; Guerra, Juliana C.; Miranda, Luana F. de; Romeiro, Carla F.D.; Souza-Fagundes, Elaine M.; Barbeira, Paulo Jorge Sanches; Beraldo, Heloísa

doi:10.1007/s10534-012-9547-5

Cited by 22 publications

(14 citation statements)

References 31 publications

(31 reference statements)

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“…The following trend of stable adduct formation with Sec was proposed: 122 > 124 > 123 > 125 = 126 . Beraldo and co‐workers reported that gold (III) complex ( 127 , Figure C) is able to inhibit the rat liver TrxR activity with an IC 50 value of 2.90 μM, and potently inhibits the growth of HL‐60, Jurkat, HCT‐116, and MCF‐7 cells . In addition, the gold (III) complex [Au(H py 2Ac4mT)Cl 2 ]ClH 2 O also inhibits 75% of rat liver TrxR activity .…”

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 94%

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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Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 94%

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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“…Gold(III) compounds have also attracted much attention for their outstanding cytotoxic activity, structural and electronic similarity (square planar, d 8 ) to platinum(II) complexes, (Gabbiani et al 2007;Lessa et al 2012;Maiore et al 2012). One of the main obstacles for their use in medicine is their low stability in physiological conditions which can be increased by coordination of multidentate ligands.…”

mentioning

confidence: 99%

Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates

et al. 2015

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Novel gold(I) and gold(III) complexes containing derivatives of D-galactose, D-ribose and D-glucono-1,5-lactone as ligands were synthesized and characterized by IR, (1)H, and (13)C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in μg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.

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“…Furthermore, the ESI + MS spectrum shows an exclusive [M] + complex ion peak with no evidence for the formation of gold(I) compounds, a common finding for gold(III) thiosemicarbazone derivatives. 14,28,29 Concerning 4-Cl stability, through observation of UV−vis-NIR absorption spectra (Supplementary Figure 1), it was possible to verify that incubation in DMSO and RPMI (10% of SBF) during 72 h could not significantly change the complex structure. Although stable in the aforementioned media, in PBS, a great decrease in the 416 nm band could lead one to erroneously believe there was the complex consumption during the stability experiment.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Organometallic Gold(III) Complex [Au(Hdamp)(L1⁴)]⁺ (L1 = SNS-Donating Thiosemicarbazone) as a Candidate to New Formulations against Chagas Disease

et al. 2019

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Chagas disease remains a serious public health concern with unsatisfactory treatment outcomes due to strain-specific drug resistance and various side effects. To identify new therapeutic drugs against Trypanosoma cruzi, we evaluated both the in vitro and in vivo activity of the organometallic gold(III) complex [Au(III)(Hdamp)(L14)]Cl (L1 = SNS-donating thiosemicarbazone), henceforth denoted 4-Cl. Our results demonstrated that 4-Cl was more effective than benznidazole (Bz) in eliminating both the extracellular trypomastigote and intracellular amastigote forms of the parasite without cytotoxic effects on mammalian cells. In in vivo assays, 4-Cl in PBS solution loses the protonation and becomes the 4-neutral. 4-Neutral reduced parasitaemia and tissue parasitism in addition to protecting the liver and heart from tissue damage at 2.8 mg/kg/day. All these changes resulted in the survival of 100% of the mice treated with the gold complex during the acute phase. Analyzing the surviving animals of the acute infection, the parasite load after 150 days of infection was equivalent to those treated with the standard dose of Bz without demonstrating the hepatotoxicity of the latter. In addition, we identified a modulation of interferon gamma (IFN-γ) levels that may be targeting the disease’s positive outcome. To the best of our knowledge, this is the first gold organometallic study that shows promise in an in vivo experimental model against Chagas disease.

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Spectroscopic and electrochemical characterization of gold(I) and gold(III) complexes with glyoxaldehyde bis(thiosemicarbazones): cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Cited by 22 publications

References 31 publications

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

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

Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates

Organometallic Gold(III) Complex [Au(Hdamp)(L1⁴)]⁺ (L1 = SNS-Donating Thiosemicarbazone) as a Candidate to New Formulations against Chagas Disease

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Spectroscopic and electrochemical characterization of gold(I) and gold(III) complexes with glyoxaldehyde bis(thiosemicarbazones): cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Cited by 22 publications

References 31 publications

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

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

Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates

Organometallic Gold(III) Complex [Au(Hdamp)(L14)]+ (L1 = SNS-Donating Thiosemicarbazone) as a Candidate to New Formulations against Chagas Disease

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Organometallic Gold(III) Complex [Au(Hdamp)(L1⁴)]⁺ (L1 = SNS-Donating Thiosemicarbazone) as a Candidate to New Formulations against Chagas Disease