Cobaltoceniumethynyl gold(<scp>i</scp>) as an unusual heterodinuclear bioorganometallic fragment to study the biological properties of alkynyl gold complexes

Vanicek, Stefan; Kopacka, Holger; Wurst, Klaus; Vergeiner, Stefan; Kankowski, Svenja; Schur, Julia; Bildstein, Benno; Ott, Ingo

doi:10.1039/c5dt04796j

Cited by 20 publications

(7 citation statements)

References 23 publications

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“…In addition, complexes 111 and 112 displayed a strong inhibition of TrxR with submicromolar potency and remarkable cytotoxicity (Table ) . A cobaltoceniumethynyl gold (I) complex ( 113 , Figure C) was reported by Ott and co‐workers in 2016, which triggered efficient cytotoxic effects in tumor cells (Table ) and inhibited TrxR activity with an IC 50 value of 0.11 μM …”

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 88%

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

Zhang

et al. 2018

Medicinal Research Reviews

127

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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: 88%

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

Zhang

et al. 2018

Medicinal Research Reviews

127

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“…Recent studies revealed that thioredoxin reductase (TrxR) plays an important role in regulating the redox balance and intracellular signaling pathways, which made it a potential target for cancer treatment. − For instance, alkynyl phosphine gold complex displays strong inhibitory effect on TrxR activities and proliferation of cancer cells. Curcumin, daily consumed by millions of people, exhibited potent irreversible inhibition on TrxR activity in a dose- and time-dependent manner. , Although a great number of complexes (mostly gold compounds) have been reported to exhibit TrxR inhibition and antiproliferative properties, iron complexes were rarely taken in consideration in this area. − Frontier researches have demonstrated that the biological response with TrxR was mainly dependent on the chelate ability of the ligand on the complex, causing different rates of ligand-exchange of the complex . However, high binding affinity of Fe(II/III) complexes with a thiol group may result in their easy binding with blood thiols, including glutathione (GSH) and albumin (BSA), which limited its bioavailability to cancer cells. − Therefore, minimizing the binding rate between blood thiols and Fe(II/III) complexes but maintaining its inhibition activity to TrxR is important in the design of new anticancer complexes.…”

Section: Introductionmentioning

confidence: 99%

Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis

et al. 2016

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Thioredoxin reductase (TrxR) is a selenoenzyme that could regulate intracellular oxidative balance and found to be overexpressed in many human tumor cells. Due to its important role in cancer progression, TrxR is becoming an attractive target in chemotherapeutic drug design. In this study, a new class of Fe(II) complexes with phenanthroline derivatives as ligands were synthesized and characterized. The mechanism of cell death induced by complex 3 revealed that the growth of cancer cells was suppressed by apoptosis and specifically inhibited the activities of TrxR. Furthermore, complex 3 exhibited brilliant antiangiogenic activity against HUVEC cells and inhibited cell migration and invasion. In addition, results of hematological analysis and H&E staining demonstrated that complex 3 has negligible toxicity on function of the major organs of mice. Taken together, this study provides a strategy for drug design to exploit Fe-based phenanthroline derivative as a chemotherapeutic agent in cancer treatment.

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“…A cobalteceniumethynyl gold(I) complex (130) has recently been described as a cytotoxic compound against HT-29 colon carcinoma, thanks to its effectivity in inhibiting TrxR activity. Nevertheless, no selectivity was observed since its activity in a non-tumor cell line (RC-124 derived from a human kidney) was similar to that measured in the cancerous cells [127].…”

Section: Gold(i) Complexesmentioning

confidence: 99%

Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment

Mármol

Medina-Quero

Rodríguez-Yoldi

et al. 2019

Cancers

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Due to the increasing incidence and high mortality associated with colorectal cancer (CRC), novel therapeutic strategies are urgently needed. Classic chemotherapy against CRC is based on oxaliplatin and other cisplatin analogues; however, platinum-based therapy lacks selectivity to cancer cells and leads to deleterious side effects. In addition, tumor resistance to oxaliplatin is related to chemotherapy failure. Gold(I) derivatives are a promising alternative to platinum complexes, since instead of interacting with DNA, they target proteins overexpressed on tumor cells, thus leading to less side effects than, but a comparable antitumor effect to, platinum derivatives. Moreover, given the huge potential of gold nanoparticles, the role of gold in CRC chemotherapy is not limited to gold(I) complexes. Gold nanoparticles have been found to be able to overcome multidrug resistance along with reduced side effects due to a more efficient uptake of classic drugs. Moreover, the use of gold nanoparticles has enhanced the effect of traditional therapies such as radiotherapy, photothermal therapy, or photodynamic therapy, and has displayed a potential role in diagnosis as a consequence of their optic properties. Herein, we have reviewed the most recent advances in the use of gold(I) derivatives and gold nanoparticles in CRC therapy.

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Cobaltoceniumethynyl gold(i) as an unusual heterodinuclear bioorganometallic fragment to study the biological properties of alkynyl gold complexes

Cited by 20 publications

References 23 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

Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis

Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment

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