Article
Chemistry, Multidisciplinary
Mingkai Chen, Wenqiang Cao, Junping Wang, Fei Cai, Liwen Zhu, Li Ma, Tianfeng Chen
Summary: This study demonstrates a new strategy to selectively inhibit thioredoxin reductase by constructing an electrophilic center, and confirms that this strategy can significantly improve the anticancer effect.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Hilke Burmeister, Pascal Dietze, Lutz Preu, Julia E. Bandow, Ingo Ott
Summary: Ruthenium(II) NHC complexes exhibited stronger antibacterial effects compared to metal-free benzimidazolium cations, particularly against Gram-positive bacteria. The inhibition of bacterial thioredoxin reductase by selected complexes suggested a potential contributing factor to their antibacterial effects.
Article
Chemistry, Inorganic & Nuclear
Sonia Infante-Tadeo, Vanessa Rodriguez-Fanjul, Cintia C. Vequi-Suplicy, Ana M. Pizarro
Summary: The passage describes the rapid hydrolysis and high basicity of complexes [Os(eta 6-arene)(C,N-phenylpyridine)Z] with chlorido or tethered oxygen as the ligand. It also reveals the structure-activity relationship between Os-CN and Os-NN complexes.
INORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Gaopan Dong, Xiaohan Ye, Shumei Wang, Wenhua Li, Rong Cai, Lupei Du, Xiaodong Shi, Minyong Li
Summary: This study reports a novel TrxR inhibitor Au-24 and its inhibitory ability to hepatocellular carcinoma in vitro and in vivo. Au-24 suppresses the proliferation of HepG2 cells through regulating multiple signaling pathways and inducing oxidative stress. In vivo experiments demonstrate that Au-24 is more effective than the traditional drug AA1 in inhibiting tumor growth.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Chemistry, Inorganic & Nuclear
Sina Katharina Goetzfried, Paul Kapitza, Caroline Marie Gallati, Anna Nindl, Monika Cziferszky, Martin Hermann, Klaus Wurst, Brigitte Kircher, Ronald Gust
Summary: The study evaluated the significance of halido ligands in halido[3-ethyl-4-phenyl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) complexes and their reactivity with model nucleophiles. The rapid reactivity of the complexes with selenocysteine suggests a potential correlation with the inhibition of thioredoxin reductase enzyme activity. Interestingly, the high-cytotoxic [(NHC)(2)Au(i)](+) complex distorted the results, indicating a complex relationship between the reactivity of the Au(I)-X bond and biological activity.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Medicinal
Rolf Buessing, Bianka Karge, Petra Lippmann, Peter G. Jones, Mark Broenstrup, Ingo Ott
Summary: The study demonstrates that gold complexes exhibit strong antibacterial effects against Gram-positive bacteria and efficiently inhibit bacterial thioredoxin reductase. Both gold(I) and gold(III) analogues show comparable efficacy in most assays.
Article
Medicine, Research & Experimental
Yiqun Xia, Jundixia Chen, Yun Yu, Fengjiao Wu, Xin Shen, Chenyu Qiu, Tingting Zhang, Lin Hong, Peisen Zheng, Rongrong Shao, Chenxin Xu, Fang Wu, Wei Chen, Congying Xie, Ri Cui, Peng Zou
Summary: The study identified a synergistic lethal interaction between mTOR and TrxR inhibitors, triggering oxidative stress and activating multiple signaling pathways to induce cancer cell death. The combination of Auranofin and Everolimus showed promising efficacy in suppressing tumor growth with minimal toxicity, suggesting a potential therapeutic strategy for cancer treatment.
Article
Biochemical Research Methods
Xiu-Fen Cheng, Nan Wang, Zhongyao Jiang, Zhenzhen Chen, Yaxin Niu, Lili Tong, Ting Yu, Bo Tang
Summary: In this study, four Au(I) complexes were screened and their target proteins were identified using an activity-based protein profiling strategy. The results showed that the target proteins of these complexes were mostly associated with cancer. Additionally, novel Au(I)-binding proteins and biological gold-protein interaction pathways were discovered.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xuefeng Liu, Hongmei Cui, Mi Li, Zuohu Chai, Haibo Wang, Xiaojie Jin, Fang Dai, Yongqi Liu, Bo Zhou
Summary: Compared to normal cells, cancer cells have intrinsic oxidative stress, making them more susceptible to the production of reactive oxygen species (ROS) by pro-oxidative anticancer agents (PAAs). However, PAAs also generate ROS in normal cells, limiting their clinical application due to narrow therapeutic window and toxic side effects. In this study, a selective ROS-generating agent, 2c, was designed using three series of dietary curcumin analogs. It showed potent selectivity in killing non-small cell lung cancer cells and inhibited tumor growth in mice. This work highlights a practical strategy of targeting thioredoxin reductase (TrxR) overexpressed in cancer cells to develop PAAs capable of generating ROS selectively.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Fernando Toshio Ogata, Alex Yuri Simoes Sato, Lucia Coppo, Roberto Jun Arai, Arnold Ira Stern, Hugo Pequeno Monteiro
Summary: The epithelial/mesenchymal transition (EMT) is associated with tumor metastasis. Cancer cells have high levels of antioxidants, such as the Trx/TrxR and GSH/Grx systems, to counteract oxidative and nitrosative stress. These systems play a significant role in EMT signaling and cancer cell progression.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Chemistry, Multidisciplinary
Mihyun Park, Claudia Schmidt, Sebastian Tuerck, Franziska Hanusch, Simone V. Hirmer, Ingo Ott, Angela Casini, Shigeyoshi Inoue
Summary: A dinuclear gold(I) complex with a strongly donating bis-N-heterocyclic imine ligand was synthesized and characterized. It showed highly selective anticancer effects against non-small cell lung cancer cells, particularly A549 cells. The anticancer effects were not correlated with the amount of gold uptake by the cells but correlated with its selective inhibition of cancer cells overexpressing a specific enzyme.
Article
Pharmacology & Pharmacy
Sahar Mazloomi, Iraj Khodadadi, Shohreh Alimohammadi, Gholamreza Shafiee
Summary: This study revealed significantly decreased activities of eNOS and TrxR enzymes in preeclampsia patients, along with markedly lower concentrations of zinc, calcium, and selenium compared to healthy controls.
CLINICAL AND EXPERIMENTAL HYPERTENSION
(2021)
Article
Agriculture, Multidisciplinary
Junmin Xi, Li-Li Tian, Jiahui Xi, Desire Girimpuhwe, Chongfei Huang, Ruixia Ma, Xiaojun Yao, Danfeng Shi, Zhongtian Bai, Quan-Xiang Wu, Jianguo Fang
Summary: This study isolated and characterized two compounds from an endophytic fungus and investigated the antitumor mechanism of one compound AP. The study found that AP inhibits the growth of liver cancer cells by targeting the selenoprotein thioredoxin reductase (TrxR) and ultimately induces cell apoptosis and ferroptosis.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Laura Hippolyte, Omar Sadek, Salem Ba Sowid, Alexandre Porcheron, Nathalie Bridonneau, Sebastien Blanchard, Marine Desage-El Murr, David Gatineau, Yves Gimbert, Dimitri Mercier, Philippe Marcus, Clement Chauvier, Corinne Chaneac, Francois Ribot, Louis Fensterbank
Summary: In this paper, a straightforward synthesis method for NHC-coated gold nanoparticles (NHC-AuNPs) is reported. The commercially available gold(I) precursor is treated with an easy-to-synthesize NHC-BH3 reagent, serving as both the reducing agent and the source of surface ligands. The strategy allows efficient control over the nucleation and growth of gold particles, resulting in a wide range of particle size variation from 4.9±0.9 to 10.0±2.7 nm. The NHC-AuNPs obtained exhibit narrow size distributions, stability over months, and do not require extensive purification or size-selectivity techniques.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Oncology
Yixuan Hu, Yinxing Zhu, Weiwei Nie, Junfeng Shi, Xiaowei Wei, Cuiju Tang, Wenwen Zhang
Summary: This study aimed to investigate the rationality and accuracy of plasma TrxR activity as a tool for early diagnosis of gastrointestinal malignancy, and its ability to evaluate therapeutic efficacy. The results showed that plasma TrxR level was significantly higher in patients with gastrointestinal malignancy, and TrxR had a high diagnostic efficiency. Additionally, the combination of TrxR and conventional tumor markers improved diagnostic efficiency. In the treatment process, the change in plasma TrxR activity was consistent with conventional tumor markers, and significantly decreased in patients receiving chemotherapy, targeted therapy, and immunotherapy.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jia Jiang, Bei Cao, Yuting Chen, Hejiang Luo, Jiaying Xue, Xiaolin Xiong, Taotao Zou
Summary: The stable alkylgold(III) complexes can undergo unprecedented photo-induced beta-hydride elimination within tumors, releasing bioactive [Au-III-S] adducts that exhibit efficient tumor-selective uptake and antitumor activities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Inorganic & Nuclear
Xiaolin Xiong, Liu-Yi Liu, Zong-Wan Mao, Taotao Zou
Summary: This article discusses the methods for deciphering the mechanism of action of metal complexes and provides selected examples with in-depth mechanistic insights.
COORDINATION CHEMISTRY REVIEWS
(2022)
Article
Chemistry, Physical
Juraj Ovcar, Tik Lun Leung, Luca Grisanti, Zeljko Skoko, Martina Vrankic, Kam-Hung Low, Shixun Wang, Pei-Ying You, Hyeyoung Ahn, Ivor Loncaric, Aleksandra B. Djurisic, Jasminka Popovic
Summary: This study investigates the influence of spacer cations on the structure of two-dimensional perovskites. The results show that the branched tert-butyl ammonium spacer cation can form a stable Ruddlesden-Popper structure when the inorganic pocket is designed appropriately.
CHEMISTRY OF MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Jinhui Wang, Xiaoshuai Sun, Yanxuan Xie, Yan Long, Huowen Chen, Xiaojun He, Taotao Zou, Zong-Wan Mao, Wei Xia
Summary: This article reports a gold(I) N-heterocyclic carbene compound that exhibits potent antibacterial activity against P. aeruginosa and has a low tendency to develop antibiotic resistance. The antibacterial mechanism of this compound involves disrupting bacterial membrane integrity, leading to high bactericidal activity against P. aeruginosa. In vitro and in vivo experiments have shown excellent therapeutic effects of this compound against P. aeruginosa infection.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Xiaolin Xiong, Ke-Bin Huang, Yuan Wang, Bei Cao, Yunli Luo, Huowen Chen, Yan Yang, Yan Long, Moyi Liu, Albert S. C. Chan, Hong Liang, Taotao Zou
Summary: This study reports a new ICD inducer and reveals its interaction with the master regulator protein BiP in the endoplasmic reticulum stress pathway. The findings of this study contribute to the understanding of the mode of action of ICD and provide important information for the design of new ICD agents with high specificity and improved efficacy.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yunli Luo, Bei Cao, Mingjie Zhong, Moyi Liu, Xiaolin Xiong, Taotao Zou
Summary: This study reports a novel approach combining photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) for cancer treatment. Cyclometalated gold(III)-alkyne complexes can achieve conditional PDT and highly efficient PACT under oxygenated and hypoxic conditions respectively, and the conditional PDT-to-PACT reactivity can be triggered by external photosensitizers, providing tumor selectivity and deep tissue penetration.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Zongshang Li, Ke Xiao, Qingyun Wan, Rui Tang, Kam-Hung Low, Xiaodong Cui, Chi-Ming Che
Summary: The introduction of multiple kinetic aggregation states (Aggs) into the self-assembly pathway can increase the complexity and flexibility of the self-assemblies. This was achieved by using a series of chiral and achiral d(10) Au-I bis(N-heterocyclic carbene, NHC) complexes, where the achiral complex could undergo self-assembly with multiple kinetic Aggs. The chiral Au-I self-assemblies exhibited nonlinear optical response of second harmonic generation (SHG) and could function as optical waveguides with strong emission polarization, while these properties were absent in the achiral analogue.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Xiaolin Xiong, Yuan Wang, Taotao Zou
Summary: The unclear molecular mechanism of small molecule-induced ICD has hindered drug development progress, but recent efforts have been made to understand the mechanisms better, with a focus on the role of unfolded protein response (UPR) and classification of inducers based on UPR dependency.
Review
Chemistry, Multidisciplinary
Jia Jiang, Xiaolin Xiong, Taotao Zou
Summary: Research on the chemistry of gold has advanced rapidly in recent decades, but translating this chemistry into living systems is challenging due to the presence of concentrated nucleophiles and reductants that can bind and quench the active gold species. Modulating the reactivity of gold complexes and activating their bioactivity at target sites is crucial for developing gold complexes for biomedical applications. Various strategies, such as structure modification, GSH-responsive prodrugs, photoactivatable prodrugs, and bioorthogonal activation, have been explored to overcome these challenges and improve the therapeutic potential of gold complexes.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Si Nga Wong, Kam-Hung Low, Yi Lam Poon, Xinyue Zhang, Ho Wan Chan, Shing Fung Chow
Summary: This study successfully synthesized a cocrystal of remdesivir (RDV) with salicylic acid (SA) through liquid-assisted grinding and thermal annealing. The molecular structure of RDV-SA was resolved through powder X-ray analysis. RDV-SA was further developed as inhaled dry powders for potential COVID-19 therapy, displaying improved release in simulated lung fluid compared to raw RDV.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Inorganic & Nuclear
Chen Wu, Kam-Hung Low, Vonika Ka-Man Au
Summary: A class of alkaline earth metal-based metal-organic frameworks (MOFs) named NDCMOF(Ca) and NDCMOF(Sr) were synthesized using 2,6-naphthalenedicarboxylic acid (NDC) as the linker. These MOFs were able to remove copper(II) ions (Cu2+) from aqueous systems and exhibited comparable adsorption capacities to other related MOFs and porous materials. Additionally, they displayed blue luminescence in the solid state at room temperature upon UV light excitation, which could be quenched after the adsorption of Cu2+ ions, making them versatile adsorbents and sensors for Cu2+ in water.
JOURNAL OF SOLID STATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Xiaoyong Mo, Yulin Deng, Samuel Kin-Man Lai, Xutao Gao, Hung-Ling Yu, Kam-Hung Low, Zhengxiao Guo, Heng-Liang Wu, Ho Yu Au-Yeung, Edmund C. M. Tse
Summary: Efficient O2 reduction reaction (ORR) for selective H2O generation can be achieved by introducing the concept of mechanical interlocking to Cu complexes. These interlocked catenane ligands can control O2 binding mode, promote electron transfer, and enhance the selectivity and activity of ORR.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Moyi Liu, Yunli Luo, Junyu Yan, Xiaolin Xiong, Xiwen Xing, Jong Seung Kim, Taotao Zou
Summary: Boronic acid (or ester) is commonly used in the development of anticancer prodrugs, but their application is hindered by low activation efficiency. In this study, a photoactivation approach was developed to convert the boronic acid-caged iridium complex into a bioactive form under hypoxic tumor microenvironments. The mechanism involves the photo-oxidation of phenyl boronate anion to generate a highly reactive phenyl radical, which can capture O2 even at low concentrations. This photoactivation approach shows potent antitumor activities in various experimental models. It can also be extended to activate prodrugs of other anticancer compounds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Lu Han, Zhiteng Luo, Yingchen Ju, Bingyi Chen, Taotao Zou, Junjian Wang, Jun Xu, Qiong Gu, Xiang-Lei Yang, Paul Schimmel, Huihao Zhou
Summary: Aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are essential enzymes in protein translation, categorized into two classes with distinct active site architectures. The orphan GlyRS in bacteria has a unique X-shaped structure. A cocrystal structure elucidates how this orphan GlyRS specifically recognizes its substrate tRNA. The X shape of orphan GlyRS suggests potential nonactive site targets for aaRS-directed antibiotics.
Article
Chemistry, Multidisciplinary
Si Nga Wong, Kam-Hung Low, Jingwen Weng, Ho Wan Chan, Shing Fung Chow
Summary: In this study, two DEX cocrystals with benzenediols (catechol and resorcinol) were successfully synthesized for the first time via mechanical treatment, providing a new approach to expand the solid-state landscape and improve the pharmaceutical properties of DEX.
