Medicinal Applications of Gold(I/III)-Based Complexes Bearing N-Heterocyclic Carbene and Phosphine Ligands

Dominelli, Bruno; Correia, João D. G.; Kühn, Fritz E.

doi:10.1016/j.jorganchem.2018.04.023

Cited by 80 publications

(44 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The activity of 3 b and 5 is superior to the known Au(I) histidinylidene complex, corroborating the previously reported correlation between lipophilicity of the wingtips and antiproliferative activity . Furthermore, both complexes 3 b and 5 show a comparable activity in the cisplatin resistant cell line A2780cisR and in the respective cisplatin sensitive cell line.…”

Section: Resultssupporting

confidence: 87%

Antiproliferative Activity of Functionalized Histidine‐derived Au(I) bis‐NHC Complexes for Bioconjugation

Jakob

Dominelli

Hahn

et al. 2020

Chemistry An Asian Journal

Self Cite

View full text Add to dashboard Cite

A series of histidine derived Au(I) bis‐NHC complexes bearing different ester, amide and carboxylic acid functionalities as well as wingtip substituents is synthesized and characterized. The stability in aqueous media, in vitro cytotoxicity in a set of cancer cell lines (MCF7, PC3 and A2780/A2780cisR) along with the cellular uptake are evaluated. Stability tests suggest hydrolysis of the ester within 8 h, which might lead to deactivation. Furthermore, the bis‐NHC system shows a sufficient stability against cysteine and the thiol containing peptide GSH. The benzyl ester and amide show the highest activity comparable to the benchmark compound cisplatin, with the ester only displaying a slightly lower cytotoxicity than the amide. A cellular uptake study revealed that the benzyl ester and the amide could have different intracellular distribution profiles but both complexes induce perturbations of the cellular physiological processes. The simple modifiability and high stability of the complexes provides a promising system for upcoming post modifications to enable targeted cancer therapy.

show abstract

Section: Resultssupporting

confidence: 87%

Antiproliferative Activity of Functionalized Histidine‐derived Au(I) bis‐NHC Complexes for Bioconjugation

Jakob

Dominelli

Hahn

et al. 2020

Chemistry An Asian Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…The selectivity of gold–NHCs complexes against cancer cells, and, indeed, other metal–carbene complexes, is most likely related to their delocalised lipophilic cationic (DLC) behaviour which favours their accumulation in cancer cells due to their relatively high mitochondrial membrane potential [ 86 , 87 , 88 , 89 ]. A very recent review described the medicinal applications of gold(I)/(III) complexes bearing N-heterocyclic carbenes [ 90 ].…”

Section: Gold(i) and Gold(iii) Compounds With Promising Anti-cancementioning

confidence: 99%

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

2018

View full text Add to dashboard Cite

A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H3N)2PtCl2], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.

show abstract

“…However, several of the proposed compounds exhibit undesirable features such as low stability leading to the rapid substitution of ligands and poor water solubility. Indeed, stability in physiological media within a reasonable timeframe and an appropriate balance between water solubility and lipophilicity, the latter favoring tumor tissue penetration and cellular uptake, are important factors. In some cases, limited ligand exchange, for example, whereby chloride ligands are replaced by water molecules, is key to the activation of the drug .…”

Section: Introductionmentioning

confidence: 99%

Anticancer Potential of Diiron Vinyliminium Complexes

Rocco

Batchelor

Agonigi

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

Although ferrocene derivatives have attracted considerable attention as possible anticancer agents, the medicinal potential of diiron complexes has remained largely unexplored. Herein, we describe the straightforward multigram‐scale synthesis and the antiproliferative activity of a series of diiron cyclopentadienyl complexes containing bridging vinyliminium ligands. IC50 values in the low‐to‐mid micromolar range were determined against cisplatin sensitive and resistant human ovarian carcinoma (A2780 and A2780cisR) cell lines. Notable selectivity towards the cancerous cells lines compared to the non‐tumoral human embryonic kidney (HEK‐293) cell line was observed for selected compounds. The activity seems to be multimodal, involving reactive oxygen species (ROS) generation and, in some cases, a fragmentation process to afford monoiron derivatives. The large structural variability, amphiphilic character and good stability in aqueous media of the diiron vinyliminium complexes provide favorable properties compared to other widely studied classes of iron‐based anticancer candidates.

show abstract

Medicinal Applications of Gold(I/III)-Based Complexes Bearing N-Heterocyclic Carbene and Phosphine Ligands

Cited by 80 publications

References 83 publications

Antiproliferative Activity of Functionalized Histidine‐derived Au(I) bis‐NHC Complexes for Bioconjugation

Antiproliferative Activity of Functionalized Histidine‐derived Au(I) bis‐NHC Complexes for Bioconjugation

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

Anticancer Potential of Diiron Vinyliminium Complexes

Contact Info

Product

Resources

About