Article
Biochemistry & Molecular Biology
Francesca Fata, Radosveta Gencheva, Qing Cheng, Rachel Lullo, Matteo Ardini, Ilaria Silvestri, Federica Gabriele, Rodolfo Ippoliti, Christina A. Bulman, Judy A. Sakanari, David L. Williams, Elias S. J. Arner, Francesco Angelucci
Summary: This study characterized the thioredoxin reductase (TrxR) selenoproteins from two filarial nematode parasites, providing insights on drug targets for lymphatic filariasis and onchocerciasis treatment.
Review
Chemistry, Inorganic & Nuclear
Shuying Shen, Jie Shen, Zhong Luo, Fudi Wang, Junxia Min
Summary: Auranofin (AUR) is a lipophilic gold-based compound used for rheumatoid arthritis treatment. It exhibits diverse biological properties, including antibacterial, antiviral, antifungal, antiparasitic, and anticancer activities. Mechanistically, AUR regulates cellular redox homeostasis by inhibiting thioredoxin reductase activity and affects multiple signaling pathways related to cell proliferation, apoptosis, and ferroptosis. Advances in stereospecific chemistry of AUR have identified new targets, offering potential for its use in various clinical indications.
COORDINATION CHEMISTRY REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Isao Momose, Takefumi Onodera, Manabu Kawada
Summary: Gold compound auranofin has been approved as a therapeutic agent for rheumatoid arthritis, but it also shows promising potential for treating other diseases such as cancer and neurodegenerative disorders. By inhibiting thioredoxin reductase, auranofin increases cellular oxidative stress and suppresses tumor growth, suggesting its potential as an anticancer agent.
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
(2021)
Review
Biochemistry & Molecular Biology
Garett J. Steers, Gloria Y. Chen, Brianne R. O'Leary, Juan Du, Hannah Van Beek, Joseph J. Cullen
Summary: Pancreatic cancer is a significant global health issue with limited progress in treatment development. Pharmacologic ascorbate (P-AscH(-)) and auranofin (Au) show promise as potential therapies for pancreatic cancer.
Article
Pharmacology & Pharmacy
Simona Braccini, Giorgia Rizzi, Lorenzo Biancalana, Alessandro Pratesi, Stefano Zacchini, Guido Pampaloni, Federica Chiellini, Fabio Marchetti
Summary: A series of novel diiron complexes were synthesized and evaluated for their anticancer activity, showing potent cytotoxicity against cancer cell lines with remarkable selectivity and good performance in inhibiting cell proliferation. Additionally, these complexes were capable of inducing significant ROS production and had the potential to inhibit the enzyme thioredoxin reductase.
Article
Biochemistry & Molecular Biology
Laurie Freire Boullosa, Jinthe Van Loenhout, Tal Flieswasser, Jorrit De Waele, Christophe Hermans, Hilde Lambrechts, Bart Cuypers, Kris Laukens, Esther Bartholomeus, Vasiliki Siozopoulou, Winnok H. De Vos, Marc Peeters, Evelien L. J. Smits, Christophe Deben
Summary: Auranofin (AF), an FDA-approved antirheumatic drug, exhibits anticancer properties by inhibiting TrxR in non-small cell lung cancer cells. Mutant p53 expression enhances sensitivity to AF and leads to various cell death mechanisms including apoptosis and ferroptosis. AF also modulates the innate immune response, enhancing natural killer cell-mediated killing and dendritic cell maturation.
Article
Biochemistry & Molecular Biology
Yana Shaulov, Lotem Sarid, Meirav Trebicz-Geffen, Serge Ankri
Summary: The study demonstrates that Auranofin-adapted Entamoeba histolytica trophozoites exhibit impaired growth, increased sensitivity to oxidative and nitrosative stress, and reduced levels of oxidative products compared to acute AF-exposed trophozoites. Additionally, overexpression of the mammalian thioredoxin reductase does not protect the parasite against AF, indicating that it is not central to the adaptation mechanism.
Article
Microbiology
LewisOscar Felix, Eleftherios Mylonakis, Beth Burgwyn Fuchs
Summary: New antibacterial compounds targeting Thioredoxin reductase (TrxR) in Gram-positive bacteria show promising bactericidal effects with minimal inhibitory concentrations comparable to or lower than standard medications, even against drug resistant isolates. Existing drug resistance mechanisms do not confer resistance to TrxR targeting compounds, suggesting potential for further exploitation of TrxR in drug development. Interaction studies between TrxR and these compounds demonstrate the development of a new antimicrobial class with direct interaction and inhibition of the validated target.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Hajar Yaakoub, Cindy Staerck, Sara Mina, Charlotte Godon, Maxime Fleury, Jean-Philippe Bouchara, Alphonse Calenda
Summary: The importance of repurposing old drugs has been highlighted in the context of slowing down the exploration of new drugs. Auranofin and honokiol have shown significant antifungal activities against Scedosporium species and Lomentospora prolificans, suggesting their potential use in combating infections caused by therapy-refractory microorganisms.
Article
Biochemistry & Molecular Biology
Xia Ying Cui, Sun Hyang Park, Woo Hyun Park
Summary: Auranofin, a thioredoxin reductase inhibitor, has anti-cancer effects in lung cancer cells by increasing ROS levels and depleting GSH.
Article
Oncology
Hideyuki Kinoshita, Osamu Shimozato, Takeshi Ishii, Hiroto Kamoda, Yoko Hagiwara, Toshinori Tsukanishi, Seiji Ohtori, Tsukasa Yonemoto
Summary: High-level expression of TXNRD-2 is a negative prognostic factor for metastasis and overall survival in osteosarcoma patients. Auranofin induces apoptosis of osteosarcoma cells via the oxidative stress-MAPK-Caspase 3 pathway and suppresses cell migration. Auranofin inhibits pulmonary metastasis of osteosarcoma, but not local progression.
ANTICANCER RESEARCH
(2021)
Article
Chemistry, Medicinal
Yukiko Miyamoto, Shubhangi Aggarwal, Jeff Joseph A. Celaje, Sozaburo Ihara, Jonathan Ang, Dmitry B. Eremin, Kirkwood M. Land, Lisa A. Wrischnik, Liangfang Zhang, Valery V. Fokin, Lars Eckmann
Summary: Diversification of gold(I) complexes can significantly improve potency against Trichomonas vaginalis, show high selectivity, and overcome resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Luisa Kober, Sebastian W. Schleser, Sofia Baer, Rainer Schobert
Summary: New mono- and di-nuclear thio-purine and thio-purine nucleoside gold(I) complexes were synthesized and evaluated for their anti-tumor activities. The introduction of different functional groups enhanced the cytotoxicity and selectivity of the complexes, which showed promising effects in inhibiting tumor-specific processes. The structure-activity relationship was explored, and the impact of different ligands on cytotoxicity was investigated. These complexes exhibited higher activity against multi-drug-resistant tumor cells and showed a dual mode of action involving cell cycle arrest and DNA repair mechanism.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Monika Szeliga, Radoslaw Rola
Summary: This study identified a considerable amount of TrxR1 protein in GBM tissues, suggested TrxR1 as an attractive drug target, and highlighted AF as a potential off-patent drug candidate in GBM therapy. Treatment with AF decreased viability of GBM cells, increased ROS levels, and its cytotoxic effect was potentiated by treatment with MEN.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Laurie Freire Boullosa, Jinthe Van Loenhout, Christophe Hermans, Ho Wa Lau, Celine Merlin, Elly Marcq, Farnaz Sedigheh Takhsha, Wim Martinet, Guido R. Y. De Meyer, Filip Lardon, Evelien L. J. Smits, Christophe Deben
Summary: This study evaluated the solvent and administration route of the thioredoxin reductase 1 (TrxR) inhibitor, auranofin (AF), in two mouse cancer models. The results showed that oral gavage was the optimal administration route for high doses of AF, and a solvent comprising 50% DMSO, 40% PEG300, and 10% ethanol improved AF's solubility in mice.
Article
Chemistry, Inorganic & Nuclear
Francesca Binacchi, Cassandra Elia, Damiano Cirri, Corjan van de Griend, Xue-Quan Zhou, Luigi Messori, Sylvestre Bonnet, Alessandro Pratesi, Tarita Biver
Summary: Metal compounds are attractive ligands for various nucleic acids. Five metal complexes with aminopyridyl-2,2'-bipyridine tetradentate ligands and quasi-planar geometry were studied for their binding to different nucleic acid molecules. The binding preferences and structural features of the metal complexes were analyzed using spectroscopy and melting methods.
DALTON TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Giovanni Canil, Juan Gurruchaga-Pereda, Simona Braccini, Lorella Marchetti, Tiziana Funaioli, Fabio Marchetti, Alessandro Pratesi, Luca Salassa, Chiara Gabbiani
Summary: Photoactivatable Pt(IV) prodrugs have great potential as metal-based drugs due to their chemical inertness in oxidized form and selective targeting compared to Pt(II) compounds. A new Pt(IV) complex, soluble in water and unreactive until reduction, was synthesized. The complex exhibited rapid and efficient photoreduction with visible light, facilitated by a catalytic system based on flavin and NADH. The reactivity of the prodrug against biological targets was only observed after photoreduction to its Pt(II) analogue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ester Giorgi, Francesca Binacchi, Carlo Marotta, Damiano Cirri, Chiara Gabbiani, Alessandro Pratesi
Summary: Despite progress, cancer still poses challenges due to side effects, resistance, and poor selectivity of current metal-based therapies. New strategies reviewed include using heterobimetallic complexes containing different metal centers and conjugating metal complexes to target cancer cells. Examples of targeting organelles and the entire cancer cell were highlighted.
Article
Biochemistry & Molecular Biology
Damiano Cirri, Andrea Geri, Lara Massai, Michele Mannelli, Tania Gamberi, Francesca Magherini, Matteo Becatti, Chiara Gabbiani, Alessandro Pratesi, Luigi Messori
Summary: A panel of four novel gold(I) complexes, inspired by the clinically established gold drug auranofin, were prepared and characterized. The differences in their interactions with model proteins were analyzed, and their cytotoxic effects on ovarian cancer cells were quantitated. These novel gold complexes showed potential as effective anticancer agents.
Article
Chemistry, Inorganic & Nuclear
Tania Hidalgo, David Fabra, Raul Allende, Ana I. Matesanz, Patricia Horcajada, Tarita Biver, Adoracion G. Quiroga
Summary: Cancer is a leading cause of death worldwide, with nearly 10 million deaths in 2020. Palladium complexes have great potential as anticancer agents, offering advantages over platinum drugs such as better speciation control and lower toxicity. This study developed two novel complexes and thoroughly investigated their speciation in solution, demonstrating their stability and behavior towards nucleic acid models and serum proteins. Furthermore, these complexes showed higher efficiency and specificity compared to the benchmark cisplatin drug due to their lower toxicity to healthy cells.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Inorganic & Nuclear
Carlo Marotta, Ester Giorgi, Francesca Binacchi, Damiano Cirri, Chiara Gabbiani, Alessandro Pratesi
Summary: The discovery of cisplatin's antineoplastic properties in 1965 renewed the interest in metal complexes for medicinal applications. Researchers have been studying safer and more effective alternatives to cisplatin, including platinum(IV)-based compounds. These compounds have attracted attention because they can be reduced in cells to activate the platinum center and offer advantages such as reducing side effects. This review summarizes the recent achievements in the field of Pt(IV) prodrugs.
INORGANICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Nadia Ribeiro, Ipek Bulut, Baris Sergi, Vivien Posa, Gabriella Spengler, Giuseppe Sciortino, Vania Andre, Liliana P. Ferreira, Tarita Biver, Valeria Ugone, Eugenio Garribba, Joao Costa-Pessoa, Eva A. Enyedy, Ceyda Acilan, Isabel Correia
Summary: This study reports the synthesis and characterization of a group of benzoylhydrazones and their Cu(II) complexes. The complexes exhibited moderate-to-strong interaction with bovine serum albumin and showed higher antiproliferative activity compared to the corresponding free ligand and cisplatin. Compound 8 demonstrated the most promising properties with low IC50 values, high induction of oxidative stress and DNA damage, resulting in high rates of apoptosis.
FRONTIERS IN CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Elisa Guazzelli, Giuseppe Pisano, Marco Turriani, Tarita Biver, Manfred Kriechbaum, Frank Uhlig, Giancarlo Galli, Elisa Martinelli
Summary: Amphiphilic copolymers with varying hydrophilic side chain lengths were synthesized and self-assembled into nanostructures in water. The thermoresponsive properties of these copolymers can be modulated by changing their chemical composition and hydrophobic component content.
Article
Chemistry, Inorganic & Nuclear
Giulio Bresciani, Serena Boni, Tiziana Funaioli, Stefano Zacchini, Guido Pampaloni, Natalia Busto, Tarita Biver, Fabio Marchetti
Summary: We synthesized and evaluated the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2-4) were obtained from the thermal reaction of [Ru2Cp2(CO)(μ-CO)(μ-η^1:η^3-C(Ph)C(Ph)C(O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc), 3-C6H4(Asp), 2-naphthyl; Cp = η(5)-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. The resulting complexes showed cytotoxic activity against cancer cells, different interactions with nucleic acids, and production of ROS.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Liyan Zhang, Peiyuan Wang, Xue-Quan Zhou, Ludovic Bretin, Xiaolong Zeng, Yurii Husiev, Ehider A. Polanco, Gangyin Zhao, Lukas S. Wijaya, Tarita Biver, Sylvia E. Le Devedec, Wen Sun, Sylvestre Bonnet
Summary: Investigation of tumor-targeting photoactivated chemotherapy using a chiral ruthenium-based anticancer warhead conjugated to an RGD-containing peptide showed strong phototoxicity and tumor-killing effects both in vitro and in vivo. The designed ruthenium-chelating peptide had triple action by preventing biomolecule coordination, self-assembling into nanoparticles, and specifically binding to tumor cells. These results demonstrate the potential of light-sensitive integrin-targeted ruthenium-based compounds for brain cancer treatment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Inorganic & Nuclear
Giarita Ferraro, Vanessa Sanfilippo, Lorenzo Chiaverini, Cristina Satriano, Tiziano Marzo, Antonello Merlino, Diego La Mendola
Summary: This study investigates the interaction between cisplatin and angiogenin and explores the impact of this interaction on prostate cancer cells. The results reveal new molecular pathways and targets for the activity of cisplatin.
DALTON TRANSACTIONS
(2023)
Review
Chemistry, Inorganic & Nuclear
Iogann Tolbatov, Elisabetta Barresi, Sabrina Taliani, Diego La Mendola, Tiziano Marzo, Alessandro Marrone
Summary: This article provides an overview of the application of diruthenium(ii,iii) paddlewheel complexes for anticancer purposes. The use of this coordinative construct allows for combining the pharmacological properties of the dimetallic ruthenium center with specific carboxylate ligands to produce new entities with improved biological profiles. These systems also enable multiple drug deliveries to the target site, but chemico-physical aspects need to be considered for effective complex design.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Biochemistry & Molecular Biology
Beatrice Campanella, Simona Braccini, Giulio Bresciani, Michele De Franco, Valentina Gandin, Federica Chiellini, Alessandro Pratesi, Guido Pampaloni, Lorenzo Biancalana, Fabio Marchetti
Summary: Diiron vinyliminium complexes are promising organometallics with potential anticancer activity. The synthesis and evaluation of [Fe2Cp2(CO)(mu-CO){mu-eta(1):eta(3)-C(R-3)C(R-4)CN(R-1)(R-2)}]CF3SO3 (2a-c, 4a-d) complexes were performed, including their solubility in D2O, Log P-ow, stability in D2O/Me2SO-d(6) mixture, and antiproliferative activity against ovarian cancer cell lines A2780 and A2780cisR, as well as the nontumoral cell line Balb/3T3 clone A31. The cytotoxicity data of 50 vinyliminium complexes were correlated with the structural properties, showing a positive correlation between octanol-water partition coefficient and relative antiproliferative activity on ovarian cancer cell lines. However, the effects of different substituents provided guidelines for the development of novel, more effective compounds. Three additional complexes (4p-r) were designed, synthesized, and biologically investigated, revealing their ability to inhibit thioredoxin reductase enzyme and induce cancer cell production of reactive oxygen species.