Article
Biochemistry & Molecular Biology
Ginevra Passeri, Joshua Northcote-Smith, Roshane Perera, Nikola Gubic, Kogularamanan Suntharalingam
Summary: This study reports a new nickel(II) complex 1 with anti-osteosarcoma stem cell (OSC) properties, which exhibits higher potency towards OSCs than current metal-based drugs, and induces necroptosis in OSCs through a cyclooxygenase-2 (COX-2) dependent mechanism.
Article
Chemistry, Multidisciplinary
Zhouyang Huang, Samantha N. N. MacMillan, Justin J. J. Wilson
Summary: In this study, a new fluorogenic mitochondrial calcium uniporter (MCU) inhibitor, RuOCou, is introduced. This compound exhibits both increased MCU-inhibitory activity and fluorescence intensity after aquation. By monitoring its fluorescence response, the aquation of RuOCou can be observed in HeLa cell lysates and live HeLa cells. This fluorogenic prodrug shows potential as a theranostic MCU inhibitor for the treatment of human diseases associated with MCU activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Jaccoline Zegers, Maartje Peters, Bauke Albada
Summary: This article summarizes the importance of stabilizing guanine quadruplexes (G4s) for cancer treatment and explores the methods and techniques for stabilizing G4s using metal complexes. By analyzing the G4-stabilizing capacity and bioactivity data of 74 metal-based ligands, guidelines for future studies in this field are proposed.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2023)
Review
Chemistry, Inorganic & Nuclear
Zhouyang Huang, Justin J. Wilson
Summary: Multimetallic Re(CO)(3) complexes show promising therapeutic and diagnostic potential in the field of biomedical research. By capitalizing on the potential synergistic effects of different metal centers, these complexes have the potential to become novel therapeutic agents and cellular imaging probes.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Review
Chemistry, Inorganic & Nuclear
Juan Amaro-Gahete, Mariia Pavliuk, Haining Tian, Dolores Esquivel, Francisco J. Romero-Salguero, Sascha Ott
Summary: A global hydrogen economy can be achieved through environmentally sustainable, safe, and cost-efficient renewable energy, with solar hydrogen production through artificial photosynthesis as a key strategy. The [FeFe]-hydrogenase enzymes found in anaerobic bacteria and green algae are highly efficient biological catalysts for hydrogen evolution, inspiring the design of synthetic catalyst systems. Various synthetic models based on the [FeFe]-hydrogenase enzyme active site have been explored for the reduction of protons to molecular hydrogen, utilizing a combination of different photocatalysis systems and components like [2Fe2S] clusters, photosensitizers, and molecular triads. The review highlights the importance of rational design in creating biomimetic catalysts for efficient hydrogen production, and the design features shared by stable and efficient photosystems.
COORDINATION CHEMISTRY REVIEWS
(2021)
Review
Biochemistry & Molecular Biology
Johannes Karges, Seth M. Cohen
Summary: The COVID-19 pandemic has resulted in over 2.5 million deaths worldwide, highlighting the urgent need for novel treatments against SARS-CoV-2. In addition to organic small molecule drug candidates, metal complexes have been suggested as potential antiviral agents.
Article
Biochemistry & Molecular Biology
Lorenzo Chiaverini, Damiano Cirri, Iogann Tolbatov, Francesca Corsi, Ilaria Piano, Alessandro Marrone, Alessandro Pratesi, Tiziano Marzo, Diego La Mendola
Summary: Ammonium trichloro (dioxoethylene-O,O ') tellurate (AS101) is a potential therapeutic prodrug with immunomodulatory properties. This study investigates the activation process of AS101 and its analogues in the presence of water. The results demonstrate that water triggers the conversion of AS101 to the pharmacologically active species, and the effect is influenced by the halogens present. The study provides valuable insights into the chemical and mechanistic implications of AS101 activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Khaled Habas, Joan J. Soldevila-Barreda, Maria Azmanova, Laia Rafols, Anais Pitto-Barry, Diana Anderson, Nicolas P. E. Barry
Summary: The study found that the two 16-electron organoruthenium complexes have no significant effect on the cell viability of human lymphocytes from healthy individuals, but induce an increase in DNA damage, presumably through oxidative stress production.
Article
Biochemistry & Molecular Biology
Maria Azmanova, Laia Rafols, Patricia A. Cooper, Colin C. Seaton, Steven D. Shnyder, Anais Pitto-Barry
Summary: This study presents the synthesis, characterization, and evaluation of the in vitro cytotoxicity of five maleonitriledithiolate-based ruthenium metal complexes with various phosphine ligands. These complexes showed promising in vitro cytotoxicity against ovarian and lung cancer cell lines, as well as no toxicity in preliminary in vivo pilot studies. The mechanism of action suggests an apoptotic pathway based on ROS production.
Article
Chemistry, Inorganic & Nuclear
Amarasooriya M. D. S. Jayawardhana, Yao-Rong Zheng
Summary: This study presents the interactions of mitochondria-damaging Pt(iv) prodrugs with cytochrome c and their therapeutic effects in cancer cells. The Pt(iv) prodrug accumulates in mitochondria, triggers damage and apoptosis, and shows superior efficacy compared to cisplatin. Cytochrome c accelerates reduction of the prodrug and enhances its proapoptotic activity.
DALTON TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Ge Mu, Ryan B. Gaynor, Baylee N. Mcintyre, Bruno Donnadieu, Sidney E. Creutz
Summary: Metalloenzymes extensively use manganese centers for oxidative catalysis, such as water oxidation. The development of bioinspired manganese complexes as improved synthetic catalysts for these processes has been a long-standing motivation. In this study, we report a series of bpy-(imidazole)(n) (n = 1 or 2) (bpy = 2,2 '-bipyridyl) ligands and their Mn2+ complexes. The structures of four Mn2+ complexes are characterized using single-crystal X-ray diffraction, revealing different coordination modes of tridentate and tetradentate ligands. Cyclic voltammetry results indicate ligand-centered reductions and metal-centered oxidations, while UV-vis spectroscopy and TD-DFT calculations show primarily ligand-centered transitions in the complexes. ESI-MS studies in solution provide evidence of ligand reorganization, suggesting complex speciation behavior. However, the low stability of the complexes in aqueous solution prevents their ultimate application as aqueous electrocatalysts. Possible reasons for the low stability and suggestions for improvement are discussed.
Review
Pharmacology & Pharmacy
Ilaria Iacobucci, Sara La Manna, Irene Cipollone, Vittoria Monaco, Luisa Cane, Flora Cozzolino
Summary: Metals play crucial roles in organisms, and the dysregulation of metals can lead to various disorders. Recently, there has been growing interest in the study of metal-drug complexes, and various approaches have been developed to investigate and improve the molecular mechanisms and delivery efficiency of metal drugs.
Article
Chemistry, Physical
Xiangyu Li, Na Li, Lan Yang, Rui Jiang, Yong He, Jian Shi, Zhong-Xing Jiang, Zhigang Yang
Summary: This study demonstrates a method using metal catalysts to control switchable nucleophilic sites, and provides a strategy to construct CF3-containing thiazoles and allenes via a multicomponent reaction. The reaction is practical and convenient, compatible with various sensitive functional groups and shows high inhibitory activities against human cancer cell lines. The CF3-containing thiazoles increase the level of reactive oxygen species in MCF-7 cells, suggesting a potential mechanism for inducing tumor cell apoptosis.
Article
Chemistry, Multidisciplinary
Jose Alberto Paris Junior, Mauricio Cavicchioli, Rachel Temperani Amaral Machado, Fernando Pavan, Douglas Hideki Nakahata, Pedro Paulo Corbi, Adao Marcos Ferreira Costa, Douglas Henrique Pereira, Antonio Carlos Massabni
Summary: This study describes a silver(I) complex with the antimycobacterial drug isoniazid, showing potential antimycobacterial activity. The ligand coordinates to the silver atom by the NH2 and C=O groups, suggesting promising future research on the Ag-inh complex as a potential agent against tuberculosis.
Article
Chemistry, Multidisciplinary
Andrea Capucciati, Enrico Monzani, Michela Sturini, Stefania Nicolis, Fabio A. Zucca, Luigi Bubacco, Marco Bortolus, Luigi Zecca, Luigi Casella
Summary: The study uses water-soluble melanin-protein-Fe/Cu conjugates derived from norepinephrine and fibrillar beta-lactoglobulin as reliable models for human brain locus coeruleus neuromelanin (NM). Iron and copper promote catecholamine oxidation and tend to remain coupled in oligonuclear aggregates. The Fe-Cu clusters are EPR silent and affect the H-1 NMR spectra of the conjugates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Emmanuelle Bignon, Tom Miclot, Alessio Terenzi, Giampaolo Barone, Antonio Monari
Summary: OAS1 is a key enzyme driving the immune response to SARS-CoV-2 infection, recognizing viral RNA and triggering the immune reaction. It has been found to have high sensitivity to the 5'-UTR region of the virus and the structure of the SL1/OAS1 complex has been elucidated, explaining its high affinity for OAS1.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Tom Miclot, Cecilia Hognon, Emmanuelle Bignon, Alessio Terenzi, Stephanie Grandemange, Giampaolo Barone, Antonio Monari
Summary: DNA integrity is crucial for genome stability and cell viability. When DNA is damaged, cells activate repair processes to maintain the normal cell cycle. However, the repair system may not always fully restore gene integrity, leading to mutations and accumulation of lesions that can cause carcinogenesis or programmed cell death. Among various types of DNA damage, strand breaks induced by ionizing radiation are the most toxic and difficult to repair, causing genomic instability. This study demonstrates that guanine-quadruplex (G4) arrangements exhibit remarkable structural stability even in the presence of strand breaks, suggesting an evolutionary cellular response to minimize the effects of ionizing radiation.
Review
Biochemistry & Molecular Biology
Tom Miclot, Aurane Froux, Luisa D'Anna, Emmanuelle Bignon, Stephanie Grandemange, Giampaolo Barone, Antonio Monari, Alessio Terenzi
Summary: In this review, the important studies on the interactions between G4s and peptides are examined, and the strengths and limitations of current analytic approaches are highlighted. It is found that the combined use of high-level molecular simulation techniques and experimental spectroscopy is the best way to design specifically tuned and selective peptides, thus controlling important biological functions.
Article
Chemistry, Inorganic & Nuclear
Luisa D'Anna, Simona Rubino, Candida Pipitone, Graziella Serio, Carla Gentile, Antonio Palumbo Piccionello, Francesco Giannici, Giampaolo Barone, Alessio Terenzi
Summary: Five metal complexes were synthesized and characterized for their interactions with DNA G-quadruplex structures. The copper complex showed the highest selectivity towards G-quadruplexes and exhibited dose-dependent cytotoxic activity in cancer cells.
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)
Article
Chemistry, Physical
Oksana Azpitarte, Ane Zudaire, Jon Uranga, Xabier Lopez, Luca Salassa, Elena Formoso, Elixabete Rezabal
Summary: The unconventional bioorthogonal catalytic activation of anticancer metal complexes by flavin and flavoproteins photocatalysis has been recently reported. The reactivity is based on a two-electron redox reaction of the photoactivated flavin. In addition, site mutagenesis has been found to modulate and improve the catalytic activity of mini Singlet Oxygen Generator protein (SOG). The redox properties of flavin and the resulting reactivity of miniSOG are modulated by specific mutations, which is consistent with experimental results.
Article
Chemistry, Inorganic & Nuclear
Juan Sanchez-Camacho, Sonia Infante-Tadeo, Ana C. Carrasco, Stefano Scoditti, A'lvaro Martinez, Fabienne Barroso-Bujans, Emilia Sicilia, Ana M. Pizarro, Luca Salassa
Summary: In this study, two new asymmetric Pt(IV) derivatives were designed and synthesized, which could be effectively activated into toxic Pt(II) species by incubation with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. One of the derivatives displayed enhanced toxicity in MDA-MB-231 breast cancer cells preincubated with ascorbate, suggesting selective triggering of oxaliplatin generation through redox activation. Covalent binding of the flavin to the Pt complex was shown to be pivotal for this effect.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Emmanuelle Bignon, Angelo Spinello, Tom Miclot, Luisa D'Anna, Cosimo Ducani, Stephanie Grandemange, Giampaolo Barone, Antonio Monari, Alessio Terenzi
Summary: This article investigates the interplay among three G4 sequences in the c-KIT proto-oncogene promoter and finds that their structural linkage favors the formation of a parallel structure for WSP. Using molecular dynamics simulations and enhanced sampling methods, they provide the first computationally resolved structure of a well-organized G4 cluster in the promoter of a crucial gene involved in cancer development. The study suggests that neighboring G4s influence their mutual three-dimensional arrangement and provide a powerful tool for predicting and interpreting complex DNA structures, which can be used as a starting point for drug discovery.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Physical
Valeria Butera, Luisa D'Anna, Simona Rubino, Riccardo Bonsignore, Angelo Spinello, Alessio Terenzi, Giampaolo Barone
Summary: In this study, the chemical shift values of the hydrogen atoms in a tetradentate N2O2-substituted Salphen ligand complexed with nickel(II), palladium(II), platinum(II), and zinc(II) were investigated using DFT calculations and H-1 NMR spectroscopy. The results showed that in the complexes involving group 10 elements, the hydrogen atoms at a shorter distance from the metal center exhibited a greater chemical shift, following the decreasing metal charge order of Ni > Pd > Pt.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
Article
Chemistry, Physical
Angelo Spinello, Luisa D'Anna, Emmanuelle Bignon, Tom Miclot, Stephanie Grandemange, Alessio Terenzi, Giampaolo Barone, Florent Barbault, Antonio Monari
Summary: The human enzyme TMPRSS2 is involved in protein maturation and post-translation and plays a crucial role in viral infections, particularly SARS-CoV-2. Through molecular modeling, we investigated the structure and dynamics of TMPRSS2 and its interaction with a lipid bilayer. We also studied the mechanism of action of a potential inhibitor and its effect on the enzyme. This study provides important insights for rational design of antiviral strategies targeting transmembrane proteases.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Polymer Science
M. Ali Aboudzadeh, Vanessa Rodriguez-Fanjul, Alessio Terenzi, Estibaliz Gonzalez de San Roman, Jose I. Miranda, Ana M. Pizarro, Luca Salassa, Fabienne Barroso-Bujans
Summary: We synthesized a macrocyclic poly(ethyleneoxide) (PEO) connected with a [Ru(bpy)(3)](2+) unit, which is a photoactive metal complex with potential biomedical applications. The PEO chain provides biocompatibility, water solubility, and topological play. The macrocycles were successfully synthesized by copper-free click cycloaddition and exhibited higher fluorescence lifetime compared to their linear analogues.
Article
Chemistry, Multidisciplinary
Laura F. Mazzei, Juan Gurruchaga-Pereda, Alvaro Martinez, Javier Calvo Martinez, Luca Salassa, Aitziber L. Cortajarena
Summary: In this study, a multifunctional hybrid was developed for controlling the delivery and activation of Pt anticancer agents in vitro. Consensus tetratricopeptide repeat protein (CTPR) was used to covalently co-anchor riboflavin (photocatalyst) and a Pt(iv) prodrug complex. The Pt-loaded flavoprotein induced a 40% reduction in PANC-1 cell viability through the photocatalytic formation of cisplatin.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Luisa D'Anna, Tom Miclot, Emmanuelle Bignon, Ugo Perricone, Giampaolo Barone, Antonio Monari, Alessio Terenzi
Summary: This study reveals the presence of a G-rich sequence, RG-2, in the genome of SARS-CoV-2 that can form a guanine-quadruplex structure and has potential as a target for antiviral drugs.