Advances in diphosphine ligand-containing gold complexes as anticancer agents

Mirzadeh, Nedaossadat; Reddy, T. Srinivasa; Bhargava, Suresh K.

doi:10.1016/j.ccr.2019.02.027

Cited by 52 publications

(35 citation statements)

References 107 publications

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“…Continuing our research into the development of gold complexes [9] for the treatment of cancer, [10][11][12][13][14][15] and inspired by the promising results obtained with complexes containing iminophosphorane ligands, we were interested in preparing cycloaurated compounds containing closelyr elated phosphine sulfide ligands. The monocyclic gold(III) compounds [AuCl 2 {k 2 -2-C 6 H 4 P(S)R 2 }] (R = Ph, NEt 2 )h ave been reported, from which the thiosalicylate derivative, [Au(1,2-SC 6 H 4 CO 2 ){k 2 -2-C 6 H 4 P(S)NEt 2 }],w as synthesized.…”

Section: Introductionmentioning

confidence: 99%

Potent and Selective Cytotoxic and Anti‐inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands

Reddy

Pooja

Privér

et al. 2019

Chemistry A European J

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Four cycloaurated phosphine sulfide complexes, [Au{k 2 -2-C 6 H 4 P(S)Ph 2 } 2 ][AuX 2 ][ X = Cl (2), Br (3), I( 4)] and [Au{k 2 -2-C 6 H 4 P(S)Ph 2 } 2 ]PF 6 (5), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological-like conditions and showede xcellent cytotoxicity against ab road range of cancerc ell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer( HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductasea nd induction of apoptosis through mitochondrial disruption. In vivo experiments in nude mice bearing HeLa xenografts showedt hat treatment with compounds 4 and 5 resulted in significant inhibition of tumorg rowth (35.8 and 46.9 %, respectively), better than that of cisplatin (29 %). The newly synthesized gold complexesw ere also evaluated for their in vitro and in vivo antiinflammatory activity through the study of lipopolysaccharide (LPS)-activated macrophages and carrageenan-induced hind paw edemainr ats, respectively.

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Section: Introductionmentioning

confidence: 99%

Potent and Selective Cytotoxic and Anti‐inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands

Reddy

Pooja

Privér

et al. 2019

Chemistry A European J

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“…The anticancer activity of this type of compound has also attracted interest due to its cytotoxic activity against cells from several tumor cell lines [ 9 , 10 , 11 ]. Among them, ovarian carcinoma [ 12 ], colorectal cancer [ 13 ], cervical epithelial carcinoma [ 14 ], and lung cancer cells [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…The anticancer activity of these gold compounds seems to follow different mechanisms than cisplatin or other Pt(II)/Pd(II) compounds, which mainly act by binding to DNA and inhibiting its replication. Gold compounds also exhibit cytotoxic activity against cisplatin-resistant cell lines [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives

et al. 2020

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Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh3)) (1) or triethylphosphine (Au(pben)(PEt3)) (2) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC50) was determined. 1 and 2 showed an IC50 of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms.

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“…Even today, platinum-based chemotherapeutics are still used in the majority of cancer treatments [10]. The gold-containing auranofin is an approved drug for the treatment of rheumatoid arthritis and is currently under investigation for its anticancer as well as antimicrobial properties [11][12][13][14][15][16]. Invigorated by these breakthrough successes, the field has expanded to many other elements in the last few decades, with complexes of titanium, iron, ruthenium, gallium, palladium, silver, gold, bismuth, and copper entering clinical trials [17][18][19][20][21][22].…”

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confidence: 99%

“…Ruthenium polypyridyl complex with light-triggered isoniazid ligand release(14) and a ruthenocene derivative of a β-lactam(15).…”

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Metal Complexes, an Untapped Source of Antibiotic Potential?

2020

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With the widespread rise of antimicrobial resistance, most traditional sources for new drug compounds have been explored intensively for new classes of antibiotics. Meanwhile, metal complexes have long had only a niche presence in the medicinal chemistry landscape, despite some compounds, such as the anticancer drug cisplatin, having had a profound impact and still being used extensively in cancer treatments today. Indeed, metal complexes have been largely ignored for antibiotic development. This is surprising as metal compounds have access to unique modes of action and exist in a wider range of three-dimensional geometries than purely organic compounds. These properties make them interesting starting points for the development of new drugs. In this perspective article, the encouraging work that has been done on antimicrobial metal complexes, mainly over the last decade, is highlighted. Promising metal complexes, their activity profiles, and possible modes of action are discussed and issues that remain to be addressed are emphasized.Antibiotics 2020, 9, 90 2 of 24 Metal-containing compounds have played a small but seminal role in medicinal chemistry of throughout the 20th century. An arsenic-containing compound, Salvarsan, was discovered at the beginning of the century and became the first effective treatment of syphilis [9]. It was however the discovery of the anticancer drug cisplatin and its successors that really kickstarted the field of inorganic medicinal chemistry. Even today, platinum-based chemotherapeutics are still used in the majority of cancer treatments [10]. The gold-containing auranofin is an approved drug for the treatment of rheumatoid arthritis and is currently under investigation for its anticancer as well as antimicrobial properties [11][12][13][14][15][16]. Invigorated by these breakthrough successes, the field has expanded to many other elements in the last few decades, with complexes of titanium, iron, ruthenium, gallium, palladium, silver, gold, bismuth, and copper entering clinical trials [17][18][19][20][21][22]. The medicinal applications of these metal complexes range from anticancer to antimalaria over to neurodegenerative diseases. Strangely, antibacterial applications are remarkably sparse in this list and the number of literature reports on metal-based antimicrobials is dwarfed by the much more frequent publications on metal-based anticancer compounds. This is surprising as metals such as bismuth and silver have long been known to possess antibacterial properties. Some medicinal products are currently available. There are however a variety of products, such as silver-coated underwear, with a more dubious scientific basis. Nevertheless, the systematic evaluation of the antimicrobial properties of metal complexes has increased in pace over the last decade, with several reports highlighting the activity and potential modes of action of metal-based antibiotics. This perspective article will discuss the major discoveries in the non-traditional field of metal complex-based antibiotic co...

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Advances in diphosphine ligand-containing gold complexes as anticancer agents

Cited by 52 publications

References 107 publications

Potent and Selective Cytotoxic and Anti‐inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands

Potent and Selective Cytotoxic and Anti‐inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands

Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives

Metal Complexes, an Untapped Source of Antibiotic Potential?

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