Recent development of gold(<scp>i</scp>) and gold(<scp>iii</scp>) complexes as therapeutic agents for cancer diseases

Lu, Yunlong; Ma, Xiaoyan; Chang, Xingyu; Liang, Zhenlin; Lv, Lin; Min, Shan; Lu, Qiuyue; Wen, Zhenfan; Gust, Ronald; Liu, Wukun

doi:10.1039/d1cs00933h

Cited by 79 publications

(71 citation statements)

References 264 publications

(317 reference statements)

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“…These studies prove that auranofin can effectively induce oxidation of Cys peptides and inhibit TrxR activity ( Jones et al, 2013 ; Liu et al, 2014 ). The success of auranofin as a cancer treatment has aroused the interest of pharmaceutical chemists in other gold(I) complexes ( Liu et al, 2022 ).…”

Section: Anti-lung Cancer Gold(i) Complexesmentioning

confidence: 99%

“…Metal-phosphine complexes have been utilized as cancer therapeutics for decades ( Marzano et al, 2010 ; Bhargava et al, 2018 ; Awuah et al, 2019 ; Sitole et al, 2020 ; Batista et al, 2021 ; Tavares et al, 2021 ; Liu et al, 2022 ). In 2003, Marchetti and co-workers described a mixed phosphine gold(I) complex 11 as a potent anticancer agent ( Marchetti et al, 2003 ), with positive anti-proliferative effects in the A549 cell line.…”

Section: Anti-lung Cancer Gold(i) Complexesmentioning

confidence: 99%

“…With the discovery of auranofin’s anticancer activity ( Figure 1 ) ( Abdalbari and Telleria, 2021 ), a new chapter exploring gold complexes as anticancer drugs was opened. Researchers have successively modified and improved the ligands bound to gold ions and synthesized many gold complexes with anticancer activity, including gold(I) and gold (III) ( Liu et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Organometallic gold(I) and gold(III) complexes for lung cancer treatment

Zhang

Fang

et al. 2022

Front. Pharmacol.

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Metal compounds, especially gold complexes, have recently gained increasing attention as possible lung cancer therapeutics. Some gold complexes display not only excellent activity in cisplatin-sensitive lung cancer but also in cisplatin-resistant lung cancer, revealing promising prospects in the development of novel treatments for lung cancer. This review summarizes examples of anticancer gold(I) and gold (III) complexes for lung cancer treatment, including mechanisms of action and approaches adopted to improve their efficiency. Several excellent examples of gold complexes against lung cancer are highlighted.

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Section: Anti-lung Cancer Gold(i) Complexesmentioning

confidence: 99%

Section: Anti-lung Cancer Gold(i) Complexesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Organometallic gold(I) and gold(III) complexes for lung cancer treatment

Zhang

Fang

et al. 2022

Front. Pharmacol.

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“…(1,7-Dihydro-6H-purine-6-selenolato) (triethylphosphane) gold(I) (10) 72.0 mg (142 µmol, 94%) from 6-selenopurine (30.0 mg, 151 µmol, 1.00 eq. ), Et 3 PAuCl (52.8 mg, 151 µmol, 1.00 eq.)…”

Section: -Selenopurinementioning

confidence: 99%

Revisiting the anticancer properties of phosphane(9-ribosylpurine-6-thiolato)gold(I) complexes and their 9H-purine precursors

et al. 2022

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New mono- and di-nuclear thio-purine and thio-purine nucleoside gold(I) complexes were synthesized, characterized, and evaluated in vitro for biological activities in comparison to related known purine complexes. By combining known anti-tumoral thio-purines with R3PAu moieties as present in auranofin, complexes with enhanced effects and selectivities were obtained, which not only act as cytostatics, but also disrupt tumor-specific processes. Their IC50 values in cytotoxicity test with tumor cell lines ranged from three-digit nanomolar to single-digit micromolar, revealing a tentative structure–activity relationship (SAR). Both the residues R2 of the phosphane ligand and R1 at C2 of the pyrimidine ring had a significant impact on the cytotoxicity. In most cases, the introduction of a ribo-furanosyl group at N9 of the purine led to a distinctly more cytotoxic complex. Most complexes were more active against multi-drug-resistant tumor cells or such lacking functional p53 when compared to the respective untreated wild type cell lines. Some nucleoside complexes displayed an interesting dose-dependent dual mode of action regarding cell cycle arrest and DNA repair mechanism. Some phosphane(purine-6-thiolato)gold (I) complexes had a stronger inhibitory effect on the thioredoxin reductase (TrxR) and on the reactive oxygen species (ROS) generation in cancer cells than is typical of other gold complexes. They also led to DNA fragmentation and showed anti-angiogenic effects. Their stability under test conditions was demonstrated by 77Se NMR monitoring of an exemplary selenopurine complex. Graphical abstract

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“…In recent years, there have been a few reports highlighting the use of transition metal complexes as anti-cancer agents and their possible anti-cancer chemotherapeutic potential ( Fricker, 1994 ; Lippard and Berg, 1994 ; Solomon et al, 1996 ; Zhang and Lippard, 2003 ; Heffeter et al, 2006 ; Que et al, 2008 ; Hanahan and Weinberg, 2011 ; Brady et al, 2014 ; Chang, 2015 ; Denoyer et al, 2015 ; Sun et al, 2022 ; Ge et al, 2022 ; Lu et al, 2022 ). Of these transition metals, copper in particular plays very important role in mammalian cells, e.g., copper homeostasis ( Denoyer et al, 2015 ; Li, 2020 ; Ge et al, 2022 ), inhibition of colorectal cancer progression with diethyldithiocarbamate-copper complex ( Huang et al, 2021 ), in vitro and in vivo use as potential anticancer and nonsteroidal anti-inflammatory (NSAIDS) therapeutics or agents ( Hussain et al, 2019 ), and use as antitumor ( Lumme et al, 1984 ) and anticancer agents ( Marzano et al, 2009 ) targeting topoisomerases I and II ( Molinaro et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugs

Cetin

Peng²,

Unruh³

et al. 2022

Front. Pharmacol.

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Breast cancer is the second type of cancer with a high probability of brain metastasis and has always been one of the main problems of breast cancer research due to the lack of effective treatment methods. Demand for developing an effective drug against breast cancer brain metastasis and finding molecular mechanisms that play a role in effective treatment are gradually increasing. However, there is no effective anticancer therapeutic drug or treatment method specific to breast cancer, in particular, for patients with a high risk of brain metastases. It is known that mTOR and HDAC enzymes play essential roles in the development of breast cancer brain metastasis. Therefore, it is vital to develop some new drugs and conduct studies toward the inhibition of these enzymes that might be a possible solution to treat breast cancer brain metastasis. In this study, a series of 1,10-phenanthroline and Prodigiosin derivatives consisting of their copper(I) complexes have been synthesized and characterized. Their biological activities were tested in vitro on six different cell lines (including the normal cell line). To obtain additional parallel validations of the experimental data, some in silico modeling studies were carried out with mTOR and HDAC1 enzymes, which are very crucial drug targets, to discover novel and potent drugs for breast cancer and related brain metastases disease.

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Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

Abstract: In this review, the recent progress in gold(i) and gold(iii) complexes are comprehensively summarized, and their anti-cancer activity and mechanism of action are documented.

Cited by 79 publications

References 264 publications

Organometallic gold(I) and gold(III) complexes for lung cancer treatment

Organometallic gold(I) and gold(III) complexes for lung cancer treatment

Revisiting the anticancer properties of phosphane(9-ribosylpurine-6-thiolato)gold(I) complexes and their 9H-purine precursors

Design, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugs

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