Advances in alkynyl gold complexes for use as potential anticancer agents

Ye, Zhibin; Jiang, Guizhi; Xu, Zhongren; Zhao, Shuang; Liu, Wukun

doi:10.1016/j.ccr.2020.213492

Cited by 59 publications

(37 citation statements)

References 175 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall structure of thaumatin-Au(NHC)Cl (with NHC = 1-butyl-3-meth ylidene) (Reprinted with permission from ref. [19] Copyright © 2016 American Ch Among the most common Au(I) compounds synthesized and teste anticancer drugs are those bearing phosphine [22], thiosugar [23], N-hetero (NHC) [24], alkynyl [25], and other sulfur-based ligands such as thiosemi (Figure 2). Overall structure of thaumatin-Au(NHC)Cl (with NHC = 1-butyl-3-methyl-imidazole-2ylidene) (see ref.…”

Section: Computational Studies Of Au(i) Metallodrugsmentioning

confidence: 99%

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

et al. 2021

View full text Add to dashboard Cite

Owing to the growing hardware capabilities and the enhancing efficacy of computational methodologies, computational chemistry approaches have constantly become more important in the development of novel anticancer metallodrugs. Besides traditional Pt-based drugs, inorganic and organometallic complexes of other transition metals are showing increasing potential in the treatment of cancer. Among them, Au(I)- and Au(III)-based compounds are promising candidates due to the strong affinity of Au(I) cations to cysteine and selenocysteine side chains of the protein residues and to Au(III) complexes being more labile and prone to the reduction to either Au(I) or Au(0) in the physiological milieu. A correct prediction of metal complexes’ properties and of their bonding interactions with potential ligands requires QM computations, usually at the ab initio or DFT level. However, MM, MD, and docking approaches can also give useful information on their binding site on large biomolecular targets, such as proteins or DNA, provided a careful parametrization of the metal force field is employed. In this review, we provide an overview of the recent computational studies of Au(I) and Au(III) antitumor compounds and of their interactions with biomolecular targets, such as sulfur- and selenium-containing enzymes, like glutathione reductases, glutathione peroxidase, glutathione-S-transferase, cysteine protease, thioredoxin reductase and poly (ADP-ribose) polymerase 1.

show abstract

Section: Computational Studies Of Au(i) Metallodrugsmentioning

confidence: 99%

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

et al. 2021

View full text Add to dashboard Cite

show abstract

“…These compounds show a remarkable stability in vitro and diverse biological properties can be induced by different ancillary ligands (L). [2][3][4] These gold complexes also display very interesting optical properties, due to both the heavy atom effect, which is able to induce phosphorescence emission, and the versatile attitude of the alkynyl moiety (behaving as π-donor, π-acceptor and σ-donor), that can tune the emission behavior in both isolated complexes [5] and molecular rods. [6] Recently, gold-alkynyl complexes have become attractive also in the framework of gold catalysis [7][8][9][10] with the discovery of the dual-activation mode (dual σ,π-catalysis).…”

Section: Introductionmentioning

confidence: 99%

Tuning the Gold(I)‐Carbon σ Bond in Gold‐Alkynyl Complexes through Structural Modifications of the NHC Ancillary Ligand: Effect on Spectroscopic Observables and Reactivity

2021

View full text Add to dashboard Cite

Understanding the features of the gold(I)-carbon σ bond and its modulation induced by an ancillary ligand has become fundamental for the purposes of ligand design, due to the increasing interest towards gold(I)-alkynyl complexes and their wide range of applications. We carry out a systematic computational analysis of 16 gold(I)-acetylide complexes bearing different N-Heterocyclic Carbenes (NHCs) as ancillary ligands [NHCÀ Au(I)À CCH]. The results show that the strength and features of the AuÀ C bond can be efficiently tuned by performing specific structural modifications on the NHC, enabling a more efficient π communication between the alkynyl and the ancillary ligand. We also demonstrate that the effect of the bond modulation can be revealed via NMR spectroscopy, as highlighted by the tight correlation between the computed nuclear shielding constants and the bonding parameters. Finally, we show that, for the dual-gold-catalyzed Bergman cyclization as case study, suitable structural modifications on the NHC ligand, which modulate the π-acidity of the metal fragment σ-coordinated to an enediyne substrate, could affect the reaction barrier and the thermodynamic stability of the product. All the reported results can be well rationalized in the framework of distortion/interaction analysis, which has been recently extended to the dual (σ,π-type) Au catalytic systems by Alabugin et al (J. Am. Chem. Soc. 2017, 137, 3406-3416).

show abstract

“…The water-solubility of phosphine ligands and the good aqueous solution stability of a few heterobimetallic alkynyl gold (I) complexes and trivalent gold (III) alkynyl complexes have made them easy chemicals to work with. Almost all of these studies are in vitro, and despite evidence of encouraging antiproliferative activity and acceptable toxicity profiles, no related complexes have entered clinical trials [5].…”

Section: Introductionmentioning

confidence: 99%

Histological Changes in Renal, Hepatic and Cardiac Tissues of Wistar Rats after 6 Weeks Treatment with Bipyridine Gold (III) Complex with Dithiocarbamate Ligands

et al. 2021

View full text Add to dashboard Cite

Bipyridine gold (III) dithiocarbamate compounds are Gold-III complexes with promising cytotoxic properties. In this study, the subacute toxicity of a Gold (III) complex with dithiocarbamate ligand was evaluated. In the acute toxicity component, an initial LD50 (38.46 mg/kg) was calculated by the administration of 50, 100, 200, 400, and 800 mg/kg of the compound to five groups of rats, respectively (n = 4 each). The sixth group was the control. The sub-acute toxicity component comprised the control group A (n = 6) and the study groups B (n = 10) and C (n = 4), which were administered 1 mL distilled water, 1/10 LD50 (3.8 mg/kg), and 1/5 LD50 (7.6 mg/kg), respectively, daily for 6 weeks. The alive animals were then sacrificed. Autopsy; preservation of renal, hepatic and cardiac tissue in buffered formalin; histopathological processing; microscopic evaluation; and comparison with the controls were sequentially conducted. In the subacute toxicity study at dosages of 3.8 mg/kg and 7.6 mg/kg, the renal tubules remained unaffected with no necrosis or vacuolization. Mild to moderate renal interstitial, hepatic capsular, lobular and portal inflammation along with mild focal hepatic vacuolization were present. At 3.8 mg/kg, the cardiac muscle fibers were unremarkable in 80% (n = 8) of the specimens, with mild focal hyalinization in 20% (n = 2) of the specimens. The same was observed in 50% (n = 2) of the specimens at 7.6 mg/kg. Variable congestion was evident in all of the groups. In the subacute toxicity study, the absence of renal tubular necrosis or vacuolization, the presence of mild inflammatory hepatic and renal alterations, and predominantly unremarkable cardiac muscle fibers suggest that Bipyridine gold (III)-dithiocarbamate is safe in animal studies and is a potential candidate for clinical trials.

show abstract

Advances in alkynyl gold complexes for use as potential anticancer agents

Cited by 59 publications

References 175 publications

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

Tuning the Gold(I)‐Carbon σ Bond in Gold‐Alkynyl Complexes through Structural Modifications of the NHC Ancillary Ligand: Effect on Spectroscopic Observables and Reactivity

Histological Changes in Renal, Hepatic and Cardiac Tissues of Wistar Rats after 6 Weeks Treatment with Bipyridine Gold (III) Complex with Dithiocarbamate Ligands

Contact Info

Product

Resources

About