Chemistry, structure, and biological roles of Au-NHC complexes as TrxR inhibitors

Karaaslan, Merve Gökşin; Aktaş, Aydın; Gürses, Canbolat; Gök, Yetkın; Ateş, Burhan

doi:10.1016/j.bioorg.2019.103552

Cited by 36 publications

(40 citation statements)

References 104 publications

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“…Without such information, it is very difficult to ensure that the probe will have a specific action mechanism. There are probes that due to their chemical structure, for instance, the presence of planar aromatic ligands, or specific metal centers such as Au I , are known to selectively interact with DNA or with enzymes like thioredoxin reductase (TrxR) respectively [20,21] . However, their biological interplay can be very different if the probes are not able to reach their assumed biological targets.…”

Section: Heterometallic Metallodrugsmentioning

confidence: 99%

“…There are probes that due to their chemical structure, for instance, the presence of planar aromatic ligands, or specific metal centers such as Au I , are known to selectively interact with DNA or with enzymes like thioredoxin reductase (TrxR) respectively. [20,21] However, their biological interplay can be very different if the probes are not able to reach their assumed biological targets. Therefore, the approach towards the development of a new drug when it comes to deliver theranostic probes is completely different.…”

Section: Heterometallic Metallodrugsmentioning

confidence: 99%

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Theranostics Through the Synergistic Cooperation of Heterometallic Complexes

2021

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Heterometallic drugs are emerging as a great alternative to conventional metallodrugs. Careful selection of different metallic fragments makes possible to enhance not only the therapeutic potential by a synergistic effect, but also to incorpore key features like traceability. Drugs that integrate traceability and therapy in one system are known as theranostic agents. In cancer research, theranostic agents are becoming increasingly important. They deliver crucial information regarding their biological interplay that can ultimately be used for optimization. The well‐established therapeutic potential of PtII‐, RuII‐ and AuI‐based drugs combined with the outstanding optical properties of d6 transition metal complexes grant the delivery of traceable metallodrugs. These species can be easily fine‐tuned through modification of their respective ligands to provide a new generation of drugs.

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Section: Heterometallic Metallodrugsmentioning

confidence: 99%

Section: Heterometallic Metallodrugsmentioning

confidence: 99%

Theranostics Through the Synergistic Cooperation of Heterometallic Complexes

2021

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“…A considerable amount of literature data reported the good anticancer activity of some metal N -heterocyclic complexes and many gold-NHC complex derivatives, and have been published for their interesting antitumor activity in the micromolar or submicromolar range, due to their antimitochondrial properties, as well as their ability to inhibit several enzymes, to induce cell death by apoptosis and cause an increase in reactive oxygen species [ 10 , 11 , 12 ]. Additionally, promising results have been recently obtained from some of us concerning the anticancer properties of several silver and gold NHC complexes [ 5 , 7 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

et al. 2022

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Over the past decade, metal complexes based on N-heterocyclic carbenes (NHCs) have attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In particular, the gold-based complexes are the focus of research efforts for the development of new anticancer compounds. Literature data and recent results, obtained by our research group, reported the design, the synthesis and the good anticancer activity of some silver and gold complexes with NHC ligands. In particular, some of these complexes were active towards some breast cancer cell lines. Considering this evidence, here we report some new Au-NHC complexes prepared in order to improve solubility and biological activity. Among them, the compounds 1 and 6 showed an interesting anticancer activity towards the breast cancer MDA-MB-231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the activity of the human topoisomerases I and II and the actin polymerization reaction. Moreover, a downregulation of vimentin expression and a reduced translocation of NF-kB into the nucleus was observed. The interference with these vital cell structures induced breast cancer cells’ death by triggering the extrinsic apoptotic pathway.

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“…However, it appears that DNA may not be the primary biological target of Au(III) complexes due to studies reporting low DNA binding affinity [ 115 ]. Although TrxR inhibition was found to be the main pathway of potent antitumor activity of many Au-NHC complexes [ 127 ], the reviewed studies on Au(III)–NHC complexes do not support this mode of action. Notwithstanding the fact that we observe a great deal of scientific interest in Au compounds as drug candidates, we still have insufficient data to describe modes of action and the mechanisms they involve [ 128 ].…”

Section: Discussionmentioning

confidence: 99%

Gold (III) Derivatives in Colon Cancer Treatment

Gurba

Taciak

Sacharczuk

et al. 2022

IJMS

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Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

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Chemistry, structure, and biological roles of Au-NHC complexes as TrxR inhibitors

Cited by 36 publications

References 104 publications

Theranostics Through the Synergistic Cooperation of Heterometallic Complexes

Theranostics Through the Synergistic Cooperation of Heterometallic Complexes

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

Gold (III) Derivatives in Colon Cancer Treatment

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