406 results on '"Luigi Messori"'
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2. The Many Lives of Auranofin: How an Old Anti-Rheumatic Agent May Become a Promising Antimicrobial Drug
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Francesca Coscione, Stefano Zineddu, Valentina Vitali, Marco Fondi, Luigi Messori, and Elena Perrin
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auranofin ,drug repurposing ,thioredoxin reductase ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Auranofin (AF) is a gold-based compound with a well-known pharmacological and toxicological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antiviral, antitumor, and antibacterial drug. In this review we focused on the antibacterial properties of AF, specifically researching the minimal inhibitory concentrations (MIC) of AF in both mono- and diderm bacteria reported so far in literature. AF proves to be highly effective against monoderm bacteria, while diderm are far less susceptible, probably due to the outer membrane barrier. We also reported the current mechanistic hypotheses concerning the antimicrobial properties of AF, although a conclusive description of its antibacterial mode of action is not yet available. Even if its mechanism of action has not been fully elucidated yet and further studies are required to optimize its delivery strategy, AF deserves additional investigation because of its unique mode of action and high efficacy against a wide range of pathogens, which could lead to potential applications in fighting antimicrobial resistance and improving therapeutic outcomes in infectious diseases.
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- 2024
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3. Description of a Non-Canonical AsPt Blue Species Originating from the Aerobic Oxidation of AP-1 in Aqueous Solution
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Damiano Cirri, Tiziano Marzo, Piero Mastrorilli, Valentina Petrelli, Stefano Todisco, Elvira De Giglio, Cristina Gellini, Marilena Ricci, Alessandro Pratesi, and Luigi Messori
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platinum blue compounds ,arsenoplatin-1 ,CP/MAS 1H-13C ,XPS ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The peculiar behavior of arsenoplatin-1, ([Pt(µ-NHC(CH3)O)2ClAs(OH)2], AP-1), in aqueous solution and the progressive appearance of a characteristic and intense blue color led us to carry out a more extensive investigation to determine the nature of this elusive chemical species, which we named “AsPt blue”. A multi-technique approach was therefore implemented to describe the processes involved in the formation of AsPt blue, and some characteristic features of this intriguing species were revealed.
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- 2024
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4. Protein Metalation by Medicinal Gold Compounds: Identification of the Main Features of the Metalation Process through ESI MS Experiments
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Andrea Geri, Lara Massai, and Luigi Messori
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gold compounds ,ESI mass spectrometry ,target proteins ,Organic chemistry ,QD241-441 - Abstract
Gold compounds form a new class of promising anticancer agents with innovative modes of action. It is generally believed that anticancer gold compounds, at variance with clinically established platinum drugs, preferentially target proteins rather than nucleic acids. The reactions of several gold compounds with a few model proteins have been systematically explored in recent years through ESI MS measurements to reveal adduct formation and identify the main features of those reactions. Here, we focus our attention on a group of five gold compounds of remarkable medicinal interest, i.e., Auranofin, Au(NHC)Cl, [Au(NHC)2]PF6, Aubipyc, and Auoxo6, and on their reactions with four different biomolecular targets, i.e., the proteins HEWL, hCA I, HSA and the C-terminal dodecapeptide of the enzyme thioredoxin reductase. Complete ESI MS data are available for those reactions due to previous experimental work conducted in our laboratory. From the comparative analysis of the ESI MS reaction profiles, some characteristic trends in the metallodrug-protein reactivity may be identified as detailed below. The main features are described and analyzed in this review. Overall, all these observations are broadly consistent with the concept that cytotoxic gold drugs preferentially target cancer cell proteins, with a remarkable selectivity for the cysteine and selenocysteine proteome. These interactions typically result in severe damage to cancer cell metabolism and profound alterations in the redox state, leading to eventual cancer cell death.
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- 2023
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5. Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780)
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Giovanni Chiappetta, Tania Gamberi, Fiorella Faienza, Xhesika Limaj, Salvatore Rizza, Luigi Messori, Giuseppe Filomeni, Alessandra Modesti, and Joelle Vinh
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Redox proteomics ,Cysteine ,Auranofin ,Gold drugs ,Ovarian cancer ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were investigated through a strategy based on simultaneous expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, metabolic changes associated with conversion to a glycolytic phenotype, induction of ER stress. The occurrence of the above cellular changes was extensively validated by performing direct biochemical assays. Our data are consistent with the concept that AF produces its effects through a multitarget mechanism that mainly affects the redox metabolism and the mitochondrial functions and results into severe ER stress. Results are discussed in the context of the current mechanistic knowledge existing on AF.
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- 2022
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6. Chemical Modification of Auranofin Yields a New Family of Anticancer Drug Candidates: The Gold(I) Phosphite Analogues
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Damiano Cirri, Andrea Geri, Lara Massai, Michele Mannelli, Tania Gamberi, Francesca Magherini, Matteo Becatti, Chiara Gabbiani, Alessandro Pratesi, and Luigi Messori
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auranofin ,metal-based drugs ,anticancer compounds ,phosphite compounds ,Organic chemistry ,QD241-441 - Abstract
A panel of four novel gold(I) complexes, inspired by the clinically established gold drug auranofin (1-Thio-β-D-glucopyranosatotriethylphosphine gold-2,3,4,6-tetraacetate), was prepared and characterized. All these compounds feature the replacement of the triethylphosphine ligand of the parent compound auranofin with a trimethylphosphite ligand. The linear coordination around the gold(I) center is completed by Cl−, Br−, I− or by the thioglucose tetraacetate ligand (SAtg). The in-solution behavior of these gold compounds as well as their interactions with some representative model proteins were comparatively analyzed through 31PNMR and ESI-MS measurements. Notably, all panel compounds turned out to be stable in aqueous media, but significant differences with respect to auranofin were disclosed in their interactions with a few leading proteins. In addition, the cytotoxic effects produced by the panel compounds toward A2780, A2780R and SKOV-3 ovarian cancer cells were quantitated and found to be in the low micromolar range, since the IC50 of all compounds was found to be between 1 μM and 10 μM. Notably, these novel gold complexes showed large and similar inhibition capabilities towards the key enzyme thioredoxin reductase, again comparable to those of auranofin. The implications of these results for the discovery of new and effective gold-based anticancer agents are discussed.
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- 2023
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7. Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs
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Lara Massai, Deborah Grifagni, Alessia De Santis, Andrea Geri, Francesca Cantini, Vito Calderone, Lucia Banci, and Luigi Messori
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COVID-19 ,nsp5 ,Mpro ,SARS-CoV-2 ,Auranofin ,gold compounds ,Microbiology ,QR1-502 - Abstract
Gold compounds have a long tradition in medicine and offer many opportunities for new therapeutic applications. Herein, we evaluated the lead compound Auranofin and five related gold(I) complexes as possible inhibitors of SARS-CoV-2 Main Protease (SARS-CoV-2 Mpro), a validated drug target for the COVID-19 disease. The investigational panel of gold compounds included Auranofin; three halido analogues, i.e., Au(PEt3)Cl, Au(PEt3)Br, and Au(PEt3)I; and two gold carbene complexes, i.e., Au(NHC)Cl and [Au(NHC)2]PF6. Notably, all these gold compounds, with the only exception of [Au(NHC)2]PF6, turned out to be potent inhibitors of the catalytic activity of SARS-CoV-2 Mpro: the measured Ki values were in the range 2.1–0.4 μM. The reactions of the various gold compounds with SARS-CoV-2 Mpro were subsequently investigated through electrospray ionization (ESI) mass spectrometry (MS) upon a careful optimization of the experimental conditions; the ESI MS spectra provided clear evidence for the formation of tight metallodrug-protein adducts and for the coordination of well defined gold-containing fragments to the SARS-CoV-2 Mpro, again with the only exception of [Au(NHC)2]PF6, The metal-protein stoichiometry was unambiguously determined for the resulting species. The crystal structures of the metallodrug- Mpro adducts were solved in the case of Au(PEt3)Br and Au(NHC)Cl. These crystal structures show that gold coordination occurs at the level of catalytic Cys 145 in the case of Au(NHC)Cl and at the level of both Cys 145 and Cys 156 for Au(PEt3)Br. Tight coordination of gold atoms to functionally relevant cysteine residues is believed to represent the true molecular basis of strong enzyme inhibition.
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- 2022
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8. Evaluation of Auranofin Loading within Ferritin Nanocages
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Rosanna Lucignano, Alessandro Pratesi, Paola Imbimbo, Daria Maria Monti, Delia Picone, Luigi Messori, Giarita Ferraro, and Antonello Merlino
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gold compounds ,metal complex ,metallodrugs ,protein metalation ,ferritin encapsulation ,anticancer activity ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Auranofin (AF), a gold(I) compound that is currently used for the treatment of rheumatoid arthritis and is in clinical trials for its promising anticancer activity, was encapsulated within the human H-chain and the horse spleen ferritin nanocages using the alkaline disassembly/reassembly protocol. The aim of the work was to highlight possible differences in their drug loading capacity and efficacy. The drug-loaded ferritins were characterized via UV-vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy to assess AF encapsulation and to define the exact amount of gold atoms trapped in the Ft cavity. The crystal structures allowed us to define the nature of AF interaction with both ferritins and to identify the gold binding sites. Moreover, the biological characterization let us to obtain preliminary information on the cytotoxic effect of AF when bound to the human H-chain.
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- 2022
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9. Reactions of Medicinal Gold(III) Compounds With Proteins and Peptides Explored by Electrospray Ionization Mass Spectrometry and Complementary Biophysical Methods
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Lara Massai, Carlotta Zoppi, Damiano Cirri, Alessandro Pratesi, and Luigi Messori
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anticancer metal complexes ,gold ,protein interaction ,mass spectrometry ,cytotoxic compounds ,Chemistry ,QD1-999 - Abstract
Electrospray ionization mass spectrometry (ESI MS) is a powerful investigative tool to analyze the reactions of metallodrugs with proteins and peptides and characterize the resulting adducts. Here, we have applied this type of approach to four experimental anticancer gold(III) compounds for which extensive biological and mechanistic data had previously been gathered, namely, Auoxo6, Au2phen, AuL12, and Aubipyc. These gold(III) compounds were reacted with two representative proteins, i.e., human serum albumin (HSA) and human carbonic anhydrase I (hCA I), and with the C-terminal dodecapeptide of thioredoxin reductase. ESI MS analysis allowed us to elucidate the nature of the resulting metal–protein adducts from which the main features of the occurring metallodrug–protein reactions can be inferred. In selected cases, MS data were integrated and supported by independent 1HNMR and UV–Vis absorption measurements to gain an overall description of the occurring processes. From data analysis, it emerges that most of the investigated gold(III) complexes, endowed with an appreciable oxidizing character, undergo quite facile reduction to gold(I); the resulting gold(I) species tightly associate with the above proteins/peptides with a remarkable selectivity for free cysteine residues. In contrast, in the case of the less-oxidizing Aubipyc complex, the gold(III) oxidation state is conserved, and a gold(III) fragment still containing the original ligand is found to be associated with the target proteins. It is notable that the C-terminal dodecapeptide of thioredoxin reductase containing the characteristic –Gly–Cys–Sec–Gly metal-binding motif is able in all cases to trigger gold(III)-to-gold(I) reduction. Our investigation allowed us to identify in detail the nature of the gold fragments that ultimately bind the protein targets and determine the exact binding stoichiometry; some insight on the reaction kinetics was also gained. Notably, a few clear correlations could be established between the structure of the metal complexes and the nature of the resulting protein adducts. The mechanistic implications of these findings are analyzed and thoroughly discussed. Overall, the present results set the stage to better understand the real target biomolecules of these gold compounds and elucidate at the atomic level their interaction modes with proteins and peptides.
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- 2020
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10. Mechanistic Insights Into the Anticancer Properties of the Auranofin Analog Au(PEt3)I: A Theoretical and Experimental Study
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Iogann Tolbatov, Damiano Cirri, Lorella Marchetti, Alessandro Marrone, Cecilia Coletti, Nazzareno Re, Diego La Mendola, Luigi Messori, Tiziano Marzo, Chiara Gabbiani, and Alessandro Pratesi
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cancer ,ESI-MS ,DFT ,auranofin ,gold ,metal-based anticancer drugs ,Chemistry ,QD1-999 - Abstract
Au(PEt3)I (AF-I hereafter), the iodide analog of the FDA-approved drug auranofin (AF hereafter), is a promising anticancer agent that produces its pharmacological effects through interaction with non-genomic targets such as the thioredoxin reductase system. AF-I is endowed with a very favorable biochemical profile showing potent in vitro cytotoxic activity against several cancer types including ovarian and colorectal cancer. Remarkably, in a recent publication, some of us reported that AF-I induces an almost complete and rapid remission in an orthotopic in vivo mouse model of ovarian cancer. The cytotoxic potency does not bring about highly severe side effects, making AF-I very well-tolerated even for higher doses, even more so than the pharmacologically active ones. All these promising features led us to expand our studies on the mechanistic aspects underlying the antitumor activity of AF-I. We report here on an integrated experimental and theoretical study on the reactivity of AF-I, in comparison with auranofin, toward relevant aminoacidic residues or their molecular models. Results point out that the replacement of the thiosugar moiety with iodide significantly affects the overall reactivity toward the amino acid residues histidine, cysteine, methionine, and selenocysteine. Altogether, the obtained results contribute to shed light into the enhanced antitumoral activity of AF-I compared with AF.
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- 2020
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11. In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study
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Damiano Cirri, Tiziano Marzo, Iogann Tolbatov, Alessandro Marrone, Francesco Saladini, Ilaria Vicenti, Filippo Dragoni, Adele Boccuto, and Luigi Messori
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SARS-CoV-2 ,COVID-19 ,antiviral drugs ,metallodrugs ,gold ,ruthenium ,Microbiology ,QR1-502 - Abstract
Metal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical application and tested them in vitro against the SARS-CoV-2 virus. The screening revealed that three compounds from the panel, i.e., the organogold(III) compound Aubipyc, the ruthenium(III) complex KP1019, and antimony trichloride (SbCl3), are endowed with notable antiviral properties and an acceptable cytotoxicity profile. These initial findings prompted us to perform a computational study to unveil the likely molecular basis of their antiviral actions. Calculations evidenced that the metalation of nucleophile sites in SARS-CoV-2 proteins or nucleobase strands, induced by Aubipyc, SbCl3, and KP1019, is likely to occur. Remarkably, we found that only the deprotonated forms of Cys and Sec residues can react favorably with these metallodrugs. The mechanistic implications of these findings are discussed.
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- 2021
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12. Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
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Francesca Sacco, Matteo Tarchi, Giarita Ferraro, Antonello Merlino, Giorgio Facchetti, Isabella Rimoldi, Luigi Messori, and Lara Massai
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platinum complexes ,mass spectrometry ,crystallography ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Three novel platinum(II) complexes bearing N-heterocyclic ligands, i.e., Pt2c, Pt-IV and Pt-VIII, were previously prepared and characterized. They manifested promising in vitro anticancer properties associated with non-conventional modes of action. To gain further mechanistic insight, we have explored here the reactions of these Pt compounds with a few model proteins, i.e., hen egg white lysozyme (HEWL), bovine pancreatic ribonuclease (RNase A), horse heart cytochrome c (Cyt-c) and human serum albumin (HSA), primarily through ESI MS analysis. Characteristic and variegate patterns of reactivity were highlighted in the various cases that appear to depend both on the nature of the Pt complex and of the interacting protein. The protein-bound Pt fragments were identified. In the case of the complex Pt2c, the adducts formed upon reaction with HEWL and RNase A were further characterized by solving the respective crystal structures: this allowed us to determine the exact location of the various Pt binding sites. The implications of the obtained results are discussed in relation to the possible mechanisms of action of these innovative anticancer Pt complexes.
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- 2021
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13. Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells
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Giulia Gorini, Francesca Magherini, Tania Fiaschi, Lara Massai, Matteo Becatti, Alessandra Modesti, Luigi Messori, and Tania Gamberi
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gold(III)-based compounds ,thioredoxin reductase ,mitochondria ,apoptosis signal pathway ,A2780 ovarian cancer cells ,Biology (General) ,QH301-705.5 - Abstract
Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in vitro toward a large number of human cancer cell lines. To expand the knowledge on the molecular mechanisms through which these gold(III) complexes trigger apoptosis in cancer cells, further studies have been performed using A2780 ovarian cancer cells as reference models. For comparative purposes, parallel studies were carried out on the gold(III) complex AuL12 (dibromo(ethylsarcosinedithiocarbamate)gold(III)), whose proapoptotic profile had been earlier characterized in several cancer cell lines. Our results pointed out that all these gold(III) compounds manifest a significant degree of similarity in their cellular and proapoptotic effects; the main observed perturbations consist of potent thioredoxin reductase inhibition, disruption of the cell redox balance, impairment of the mitochondrial membrane potential, and induction of associated metabolic changes. In addition, evidence was gained of the remarkable contribution of ASK1 (apoptosis-signal-regulating kinase-1) and AKT pathways to gold(III)-induced apoptotic signaling. Overall, the observed effects may be traced back to gold(III) reduction and subsequent formation and release of gold(I) species that are able to bind and inhibit several enzymes responsible for the intracellular redox homeostasis, in particular the selenoenzyme thioredoxin reductase.
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- 2021
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14. Cyclodextrin Inclusion Complexes of Auranofin and Its Iodido Analog: A Chemical and Biological Study
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Damiano Cirri, Ida Landini, Lara Massai, Enrico Mini, Francesca Maestrelli, and Luigi Messori
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auranofin ,metal-based drugs ,cyclodextrin encapsulation ,Pharmacy and materia medica ,RS1-441 - Abstract
Auranofin (AF) and its iodido analog, i.e., Au(PEt3) I (AFI), were reported to exhibit very promising anticancer properties both in vitro and in vivo. However, both these gold compounds have a scarce aqueous solubility that hampers their pharmaceutical use. Here, we explore whether encapsulation of these metallodrugs inside hydroxypropyl-beta–cyclodextrin (HPβ–CD) may lead to an improved biopharmaceutical profile for the resulting adducts. Phase solubility studies, performed at 25 °C in an aqueous buffer, revealed, in both cases, the formation of a 1:1 drug to cyclodextrin complex; a far greater apparent stability constant (K1:1) was measured for AFI compared to AF (331 M−1 versus ca. 30 M−1). NMR studies conducted on the AFI/HPβ–CD system confirmed the formation of a stable 1:1 adduct. Then, binary systems of AF and AFI with HPβ–CD were prepared by colyophilization and characterized by DSC and PXRD. The results revealed the occurrence of drug complexation and/or amorphization for the AFI/HPβ–CD binary system. Afterwards, the antiproliferative properties of the two cyclodextrin adducts and of the corresponding free drugs were comparatively evaluated in vitro in three representative ovarian cancer cell lines, i.e., A2780, SKOV3, and IGROV-1. The results, in all cases, point out that CD complexation of the two gold drugs does not substantially affect their biological activity. The implications of these findings are discussed in the frame of the current knowledge of AF and its analogs.
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- 2021
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15. Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity
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Giarita Ferraro, Alessandro Pratesi, Damiano Cirri, Paola Imbimbo, Daria Maria Monti, Luigi Messori, and Antonello Merlino
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Pt compounds ,metal complexes ,metallodrugs ,As compounds ,protein metalation ,ferritin encapsulation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.
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- 2021
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16. On the Different Mode of Action of Au(I)/Ag(I)-NHC Bis-Anthracenyl Complexes Towards Selected Target Biomolecules
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Francesca Binacchi, Federica Guarra, Damiano Cirri, Tiziano Marzo, Alessandro Pratesi, Luigi Messori, Chiara Gabbiani, and Tarita Biver
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silver carbene ,gold carbene ,target selectivity ,nucleic acids ,quadruplexes ,mode of action ,Organic chemistry ,QD241-441 - Abstract
Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multiple techniques are here used to unveil the mechanistic details of the binding to different biosubstrates of bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride [Ag(EIA)2]Cl and bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) gold chloride [Au(EIA)2]Cl. As the biosubstrates, we tested natural double-stranded DNA, synthetic RNA polynucleotides (single-poly(A), double-poly(A)poly(U) and triple-stranded poly(A)2poly(U)), DNA G-quadruplex structures (G4s), and bovine serum albumin (BSA) protein. Absorbance and fluorescence titrations, mass spectrometry together with melting and viscometry tests show significant differences in the binding features between silver and gold compounds. [Au(EIA)2]Cl covalently binds BSA. It is here evidenced that the selectivity is high: low affinity and external binding for all polynucleotides and G4s are found. Conversely, in the case of [Ag(EIA)2]Cl, the binding to BSA is weak and relies on electrostatic interactions. [Ag(EIA)2]Cl strongly/selectively interacts only with double strands by a mechanism where intercalation plays the major role, but groove binding is also operative. The absence of an interaction with triplexes indicates the major role played by the geometrical constraints to drive the binding mode.
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- 2020
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17. Antiproliferative Properties of a Few Auranofin-Related Gold(I) and Silver(I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin Proteasome System
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Damiano Cirri, Tanja Schirmeister, Ean-Jeong Seo, Thomas Efferth, Lara Massai, Luigi Messori, and Nicola Micale
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auranofin ,metal complexes ,proteasome inhibition ,leukemia cells ,antiproliferative properties ,Organic chemistry ,QD241-441 - Abstract
A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these metal compounds were assessed against two leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against leukemia cells, with IC50 values generally falling in the low-micromolar range, the gold derivatives being on the whole more effective than the silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compounds to inhibit the three main catalytic activities of the proteasome was investigated. Different patterns of enzyme inhibition emerged for the various metal complexes. Notably, gold compounds were able to inhibit effectively both the trypsin-like and chymotrypsin-like proteasome activities, being less effective toward the caspase-like catalytic activity. In most cases, a significant selectivity of the study compounds toward the proteasome proteolytic activities was detected when compared to other proteases. The implications of the obtained results are discussed.
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- 2020
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18. Rapid purification of gold nanorods for biomedical applications
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Federica Scaletti, Chang Soo Kim, Luigi Messori, and Vincent M. Rotello
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Selective separation of gold nanorods from by-products ,Science - Abstract
Small gold nanorods (GNRs) with longitudinal plasmon absorption in the near-infrared window (700–900 nm) are of great interest for in vivo optical applications (e.g., photothermal therapy) and for their high-payload-to-carrier ratio for drug delivery. Common synthetic strategies for GNR production afford spherical and cubical nanoparticles in addition to the desired GNRs. Thus, several methods have been proposed for the selective separation of GNRs from the reaction by-products. For example, centrifugation has been used to separate the high aspect ratio (AR) GNRs (AR > 4). However, it is difficult to separate small sized GNRs with low AR (AR ≤ 4) that are particularly promising for biomedical applications. Here, we describe a simple and fast procedure for the separation of small GNRs with AR of 4, and length of 28 nm from reaction by-products. The shape separation is achieved through centrifugation according to the following steps: • Isolation of all gold products of the reaction from the excess of cetyltrimethylammonium bromide through a first cycle of centrifugation. • Optimization of the speed and the time of centrifugation for the separation of GNRs from the reaction by-products. • Shape separation of GNRs through a second cycle of centrifugation. The effectiveness of this procedure is documented.
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- 2014
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19. NAMI-A and KP1019/1339, Two Iconic Ruthenium Anticancer Drug Candidates Face-to-Face: A Case Story in Medicinal Inorganic Chemistry
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Enzo Alessio and Luigi Messori
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anticancer ,antimetastasis ,uptake ,protein binding ,ruthenium ,clinical study ,biodistribution ,activation ,aquation ,Organic chemistry ,QD241-441 - Abstract
NAMI-A ((ImH)[trans-RuCl4(dmso-S)(Im)], Im = imidazole) and KP1019/1339 (KP1019 = (IndH)[trans-RuCl4(Ind)2], Ind = indazole; KP1339 = Na[trans-RuCl4(Ind)2]) are two structurally related ruthenium(III) coordination compounds that have attracted a lot of attention in the medicinal inorganic chemistry scientific community as promising anticancer drug candidates. This has led to a considerable amount of studies on their respective chemico-biological features and to the eventual admission of both to clinical trials. The encouraging pharmacological performances qualified KP1019 mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers, whereas the non-cytotoxic NAMI-A has gained the reputation of being a very effective antimetastatic drug. A critical and strictly comparative analysis of the studies conducted so far on NAMI-A and KP1019 allows us to define the state of the art of these experimental ruthenium drugs in terms of the respective pharmacological profiles and potential clinical applications, and to gain some insight into the inherent molecular mechanisms. Despite their evident structural relatedness, deeply distinct biological and pharmacological profiles do emerge. Overall, these two iconic ruthenium complexes form an exemplary and unique case in the field of medicinal inorganic chemistry.
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- 2019
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20. Reaction with Proteins of a Five-Coordinate Platinum(II) Compound
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Giarita Ferraro, Tiziano Marzo, Maria Elena Cucciolito, Francesco Ruffo, Luigi Messori, and Antonello Merlino
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five-coordinate Pt complexes ,anticancer platinum compounds ,protein metal coordination ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein⁻metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species.
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- 2019
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21. Large Protein Assemblies for High-Relaxivity Contrast Agents: The Case of Gadolinium-Labeled Asparaginase
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Giulia Licciardi, Domenico Rizzo, Maria Salobehaj, Lara Massai, Andrea Geri, Luigi Messori, Enrico Ravera, Marco Fragai, and Giacomo Parigi
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Pharmacology ,Organic Chemistry ,Biomedical Engineering ,Contrast Media ,Asparaginase ,Pharmaceutical Science ,Gadolinium ,Bioengineering ,Magnetic Resonance Imaging ,Chelating Agents ,Biotechnology - Abstract
Biologics are emerging as the most important class of drugs and are used to treat a large variety of pathologies. Most of biologics are proteins administered in large amounts, either by intramuscular injection or by intravenous infusion. Asparaginase is a large tetrameric protein assembly, currently used against acute lymphoblastic leukemia. Here, a gadolinium(III)-DOTA derivative has been conjugated to asparaginase, and its relaxation properties have been investigated to assess its efficiency as a possible theranostic agent. The field-dependent
- Published
- 2022
22. Exploiting the Chemical Diversity of Metal Compounds as a Source of Novel Anti-COVID-19 Drugs
- Author
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Damiano Cirri, Carlo Marotta, Alessandro Pratesi, Tiziano Marzo, and Luigi Messori
- Published
- 2023
23. Dirhodium tetraacetate binding to a B-DNA double helical dodecamer probed by X-ray crystallography and mass spectrometry
- Author
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Gabriella Tito, Romualdo Troisi, Giarita Ferraro, Andrea Geri, Lara Massai, Luigi Messori, Filomena Sica, and Antonello Merlino
- Subjects
Inorganic Chemistry - Abstract
The reaction of the cytotoxic compound dirhodium tetraacetate with a B-DNA double helical dodecamer was studied by X-ray crystallography and mass spectrometry.
- Published
- 2023
24. Protein targets for anticancer metal based drugs
- Author
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Tiziano Marzo and Luigi Messori
- Published
- 2023
25. Comparative NMR metabolomics of the responses of A2780 human ovarian cancer cells to clinically established Pt-based drugs
- Author
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Veronica Ghini, Francesca Magherini, Lara Massai, Luigi Messori, and Paola Turano
- Subjects
Ovarian Neoplasms ,Inorganic Chemistry ,Organoplatinum Compounds ,Drug Resistance, Neoplasm ,Cell Line, Tumor ,Humans ,Antineoplastic Agents ,Female ,Cisplatin - Abstract
Pt-Based drugs play a very important role in current cancer treatments; yet, their cellular and mechanistic aspects are not fully understood. NMR metabolomics provides a powerful tool to investigate the metabolic perturbations induced by Pt drugs in cancer cells and decipher their meaning in relation to the presumed molecular mechanisms. We have carried out a systematic and comparative
- Published
- 2022
26. Reactions of proteins with a few organopalladium compounds of medicinal interest
- Author
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Lara Massai, Thomas Scattolin, Matteo Tarchi, Fabiano Visentin, and Luigi Messori
- Subjects
Settore CHIM/03 - Chimica Generale e Inorganica ,General Chemical Engineering ,General Chemistry ,Palladium metal drugs matal drugs-protein interactions Mass spectroscopy - Abstract
Pd compounds form a promising class of experimental anticancer drug candidates whose mechanism of action is still largely unknown; in particular, a few organopalladium compounds seem very attractive. To gain mechanistic insight into medicinal palladium compounds, we have explored here - through ESI MS analysis - the interactions of four organopalladium agents (1-4) - showing remarkable
- Published
- 2022
27. Synthesis, chemical characterization, and biological evaluation of a novel auranofin derivative as an anticancer agent
- Author
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Damiano Cirri, Lara Massai, Chiara Giacomelli, Maria Letizia Trincavelli, Annalisa Guerri, Chiara Gabbiani, Luigi Messori, and Alessandro Pratesi
- Subjects
Ovarian Neoplasms ,Inorganic Chemistry ,Auranofin ,Cell Line, Tumor ,Humans ,Antineoplastic Agents ,Female ,Gold - Abstract
A novel gold(I) complex inspired by the known medicinal inorganic compounds auranofin and thimerosal, namely ethylthiosalicylate(triethylphosphine)gold(I) (AFETT hereafter), was synthesized and characterised and its structure was resolved through X-ray diffraction. The solution behavior of AFETT and its interactions with two biologically relevant proteins (
- Published
- 2022
28. A biophysical study of the interactions of palladium(II), platinum(II) and gold(III) complexes of aminopyridyl-2,2'-bipyridine ligands with RNAs and other nucleic acid structures
- Author
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Francesca Binacchi, Cassandra Elia, Damiano Cirri, Corjan Van de Griend, Xue-Quan Zhou, Luigi Messori, Sylvestre Bonnet, Alessandro Pratesi, and Tarita Biver
- Subjects
Inorganic Chemistry - Abstract
Metal compounds form an attractive class of ligands for a variety of nucleic acids. Five metal complexes bearing aminopyridyl-2,2'-bipyridine tetradentate ligands and possessing a quasi-planar geometry were challenged toward different types of nucleic acid molecules including RNA polynucleotides in the duplex or triplex form, an RNA Holliday four-way junction, natural double helix DNA and a DNA G-quadruplex. The binding process was monitored comparatively using different spectroscopic and melting methods. The binding preferences that emerge from our analysis are discussed in relation to the structural features of the metal complexes.
- Published
- 2022
29. NMR reveals the metabolic changes induced by auranofin in A2780 cancer cells: evidence for glutathione dysregulation
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Tommaso Senzacqua, Paola Turano, Luigi Messori, Tania Gamberi, Lara Massai, and Veronica Ghini
- Subjects
Drug ,Auranofin ,media_common.quotation_subject ,Molecular Conformation ,Antineoplastic Agents ,Pharmacology ,Inorganic Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,Tumor Cells, Cultured ,medicine ,Humans ,Mode of action ,Nuclear Magnetic Resonance, Biomolecular ,Nmr based metabolomics ,030304 developmental biology ,media_common ,0303 health sciences ,Glutathione ,chemistry ,030220 oncology & carcinogenesis ,Cancer cell ,Metabolic profile ,medicine.drug - Abstract
NMR metabolomics represents a powerful tool to characterize the cellular effects of drugs and gain detailed insight into their mode of action. Here, we have exploited NMR metabolomics to illustrate the changes in the metabolic profile of A2780 ovarian cancer cells elicited by auranofin (AF), a clinically approved gold drug now repurposed as an anticancer agent. An early and large increase in intracellular glutathione is highlighted as the main effect of the treatment accompanied by small but significant changes in the levels of a few additional metabolites; the general implications of these findings are discussed in the frame of the current mechanistic knowledge of AF.
- Published
- 2021
30. Comparative reactivity of medicinal gold(<scp>i</scp>) compounds with the cyclic peptide vasopressin and its diselenide analogue
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Lara Massai, Emmanuelle Cordeau, Luisa Ronga, Ryszard Lobinski, Jeremy Lamarche, Luigi Messori, Christine Enjalbal, Enrique Alcoceba Álvarez, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Pau et des Pays de l'Adour (UPPA), and ANR-16-IDEX-0002,E2S,E2S(2016)
- Subjects
Auranofin ,Vasopressins ,Reducing agent ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Selenium compounds ,Inorganic Chemistry ,Diselenide ,Selenium ,[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,Organoselenium Compounds ,medicine ,Humans ,Reactivity (chemistry) ,Lewis acids and bases ,Protein Precursors ,Neurophysins ,chemistry.chemical_classification ,010405 organic chemistry ,[CHIM.MATE]Chemical Sciences/Material chemistry ,Sulfur ,Combinatorial chemistry ,Cyclic peptide ,0104 chemical sciences ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,[CHIM.POLY]Chemical Sciences/Polymers ,Reducing agents ,chemistry ,Organogold Compounds ,Gold compounds ,medicine.drug - Abstract
International audience; The reactions of the medicinal gold(i) compound auranofin and its close analogues with vasopressin and the diselenide analogue were comparatively investigated by LC-electrospray MS/MS. Evidence is gained of the possible cleavage of the S-S and Se-Se bridges induced by Au(i). Notably, we found that, in the absence of reducing agents, the sulfur and selenium atoms are metallated only at high temperature (70 °C) with the preferential binding of gold to selenium. The reaction with the S-S bridge can take place at physiological temperature (37 °C) under reducing conditions. The implications of these results are discussed in the general frame of the reactivity of biologically relevant soft Lewis acids with peptides and proteins.
- Published
- 2021
31. The first step of arsenoplatin-1 aggregation in solution unveiled by solving the crystal structure of its protein adduct
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Giarita Ferraro, Alessandro Pratesi, Damiano Cirri, Luigi Messori, Antonello Merlino, Tiziano Marzo, Ferraro, G., Cirri, D., Marzo, T., Pratesi, A., Messori, L., and Merlino, A.
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Aqueous solution ,Molecular Structure ,Arsenites ,chemistry.chemical_element ,Antineoplastic Agents ,Trimer ,Crystal structure ,Oligomer ,Adduct ,Solutions ,Inorganic Chemistry ,chemistry.chemical_compound ,Crystallography ,Arsenic Trioxide ,chemistry ,Coordination Complexes ,Moiety ,Muramidase ,Cisplatin ,Lysozyme ,Platinum ,Protein Binding - Abstract
Arsenoplatin-1 (AP-1) is an innovative dual-action anticancer agent that contains a platinum(ii) center coordinated to an arsenous acid moiety. We found that AP-1 spontaneously aggregates in aqueous solutions generating oligomeric species of increasing length. Afterward, we succeeded in solving the crystal structure of the adduct formed between the model protein lysozyme and an early AP-1 oligomer that turned out to be a trimer. Remarkably, this crystal structure traps an early stage of AP-1 aggregation offering detailed insight into the molecular process of the oligomer's growth.
- Published
- 2021
32. Selenol (-SeH) as a target for mercury and gold in biological systems: Contributions of mass spectrometry and atomic spectroscopy
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Mikel Bernabeu de Maria, Jérémy Lamarche, Luisa Ronga, Luigi Messori, Joanna Szpunar, and Ryszard Lobinski
- Subjects
Inorganic Chemistry ,Materials Chemistry ,Physical and Theoretical Chemistry - Published
- 2023
33. Computationally enhanced X-ray diffraction analysis of a gold(III) complex interacting with the human telomeric DNA G-quadruplex. Unravelling non-unique ligand positioning
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Damiano Cirri, Carla Bazzicalupi, Ulf Ryde, Justin Bergmann, Francesca Binacchi, Alessio Nocentini, Alessandro Pratesi, Paola Gratteri, and Luigi Messori
- Subjects
Triazines ,Quantum refinement ,Biochemistry and Molecular Biology ,DNA G-quadruplex ,General Medicine ,DNA ,Telomere ,Ligands ,Biochemistry ,QM/MM ,X-ray diffraction ,G-Quadruplexes ,X-Ray Diffraction ,Structural Biology ,Melting experiments ,Humans ,Gold ,Gold complexes ,Molecular Biology - Abstract
The crystal structure of the human telomeric DNA Tel24 G-quadruplex (Tel24 = TAG3(T2AG3)3T) in complex with the novel [AuL] species (with L = 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine - TPymT-α) was solved by a novel joint molecular mechanical (MM)/quantum mechanical (QM) innovative approach. The quantum-refinement crystallographic method (crystallographic refinement enhanced with quantum mechanical calculation) was adapted to treat the [AuL]/G-quadruplex structure, where each gold complex in the binding site was found spread over four equally occupied positions. The four positions were first determined by docking restrained to the crystallographically determined metal ions' coordinates. Then, the quantum refinement method was used to resolve the poorly defined density around the ligands and improve the crystallographic determination, revealing that the binding preferences of this metallodrug toward Tel24 G-quadruplex arise from a combined effect of pyrimidine stacking, metal–guanine interactions and charge–charge neutralizing action of the π-acid triazine. The occurrence of interaction in solution with the Tel24 G-quadruplex DNA was further proved through DNA melting experiments, which showed a slight destabilisation of the quadruplex upon adduct formation.
- Published
- 2022
34. Reactions of Arsenoplatin-1 with Protein Targets: A Combined Experimental and Theoretical Study
- Author
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Iogann Tolbatov, Damiano Cirri, Matteo Tarchi, Tiziano Marzo, Cecilia Coletti, Alessandro Marrone, Luigi Messori, Nazzareno Re, and Lara Massai
- Subjects
Inorganic Chemistry ,Arsenic Trioxide ,Physical and Theoretical Chemistry ,Cisplatin ,arsenopaltin protein targets - Abstract
Arsenoplatin-1 (AP-1) is a dual-action anticancer metallodrug with a promising pharmacological profile that features the simultaneous presence of a cisplatin-like center and an arsenite center. We investigated its interactions with proteins through a joint experimental and theoretical approach. The reactivity of AP-1 with a variety of proteins, including carbonic anhydrase (CA), superoxide dismutase (SOD), myoglobin (Mb), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and human serum albumin (HSA), was analyzed by means of electrospray ionization mass spectrometry (ESI MS) measurements. In accordance with previous observations, ESI MS experiments revealed that the obtained metallodrug-protein adducts originated from the binding of the [(AP-1)-Cl]
- Published
- 2022
35. The effects of two gold-N-heterocyclic carbene (NHC) complexes in ovarian cancer cells: a redox proteomic study
- Author
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Lara Massai, Luigi Messori, Andrea Carpentieri, Angela Amoresano, Chiara Melchiorre, Tania Fiaschi, Alessandra Modesti, Tania Gamberi, Francesca Magherini, Massai, L., Messori, L., Carpentieri, A., Amoresano, A., Melchiorre, C., Fiaschi, T., Modesti, A., Gamberi, T., and Magherini, F.
- Subjects
Pharmacology ,Ovarian Neoplasms ,Proteomics ,Cancer Research ,Redox proteomic ,Antineoplastic Agents ,Carbene complexe ,Carcinoma, Ovarian Epithelial ,Toxicology ,Gold Compounds ,Oncology ,Coordination Complexes ,Ovarian cancer ,Cell Line, Tumor ,Humans ,Pharmacology (medical) ,Female ,Gold ,Methane ,Oxidation-Reduction ,Gold drug - Abstract
Purpose Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Standard treatment consists of tumor debulking surgery followed by platinum and paclitaxel chemotherapy; yet, despite the initial response, about 70–75% of patients develop resistance to chemotherapy. Gold compounds represent a family of very promising anticancer drugs. Among them, we previously investigated the cytotoxic and pro-apoptotic properties of Au(NHC) and Au(NHC)2PF6, i.e., a monocarbene gold(I) complex and the corresponding bis(carbene) complex. Gold compounds are known to alter the redox state of cells interacting with free cysteine and selenocysteine residues of several proteins. Herein, a redox proteomic study has been carried out to elucidate the mechanisms of cytotoxicity in A2780 human ovarian cancer cells. Methods A biotinylated iodoacetamide labeling method coupled with mass spectrometry was used to identify oxidation-sensitive protein cysteines. Results Gold carbene complexes cause extensive oxidation of several cellular proteins; many affected proteins belong to two major functional classes: carbohydrate metabolism, and cytoskeleton organization/cell adhesion. Among the affected proteins, Glyceraldehyde-3-phosphate dehydrogenase inhibition was proved by enzymatic assays and by ESI–MS studies. We also found that Au(NHC)2PF6 inhibits mitochondrial respiration impairing complex I function. Concerning the oxidized cytoskeletal proteins, gold binding to the free cysteines of actin was demonstrated by ESI–MS analysis. Notably, both gold compounds affected cell migration and invasion. Conclusions In this study, we deepened the mode of action of Au(NHC) and Au(NHC)2PF6, identifying common cellular targets but confirming their different influence on the mitochondrial function.
- Published
- 2022
36. Protein Metalation by Inorganic Anticancer Drugs
- Author
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Giarita Ferraro, Tiziano Marzo, Luigi Messori, and Antonello Merlino
- Subjects
Metalation ,Chemistry ,medicine ,Cancer ,Bioinorganic chemistry ,medicine.disease ,Combinatorial chemistry - Published
- 2020
37. Medicinal Au(I) compounds targeting urease as prospective antimicrobial agents: unveiling the structural basis for enzyme inhibition
- Author
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Luigi Messori, Michele Cianci, Stefano Ciurli, Lara Massai, Luca Mazzei, and Luca Mazzei, Lara Massei, Michele Cianci, Luigi Messori, Stefano Ciurli
- Subjects
Models, Molecular ,Auranofin ,Sporosarcina ,Urease ,Urease, Nickel, X-ray crystallography, Gold-based medicinal chemistry ,Stereochemistry ,Microbial Sensitivity Tests ,Crystallography, X-Ray ,Catalysis ,Inorganic Chemistry ,Gold Compounds ,medicine ,Enzyme Inhibitors ,IC50 ,Density Functional Theory ,chemistry.chemical_classification ,biology ,Molecular Structure ,Antimicrobial ,Enzyme assay ,Anti-Bacterial Agents ,Enzyme ,chemistry ,biology.protein ,Organogold Compounds ,medicine.drug - Abstract
A few gold compounds were recently found to show antimicrobial properties in vitro, holding great promise for the discovery of new drugs to overcome antibiotic resistance. Here, the inhibition of the bacterial virulence factor urease by four Au(I)-compounds, namely Au(PEt3)Cl, Au(PEt3)Br, Au(PEt3)I and [Au(PEt3)2]Cl, obtained from the antiarthritic Au(I)-drug Auranofin and earlier reported to act as antimicrobials, is investigated. The three monophosphino Au(I) complexes showed IC50 values in the 30–100 nM range, while the diphosphino Au(I) complex, though being less active, still showed a IC50 value of 7 μM. The structural basis for this inhibition was provided by solving the crystal structures of urease co-crystallized with Au(PEt3)I and [Au(PEt3)2]Cl: at least two Au(I) ions bind the enzyme in a flap domain involved in the catalysis, thus obliterating enzyme activity. Peculiar changes observed in the two structures reveal implications for the mechanism of soft metal binding and enzyme inactivation.
- Published
- 2021
38. Direct detection of iron clusters in L ferritins through ESI-MS experiments
- Author
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Luigi Messori, Silvia Ciambellotti, Lucrezia Cosottini, Paola Turano, Alessandro Pratesi, and Lara Massai
- Subjects
Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,biology ,Chemistry ,Electrospray ionization ,Iron ,Nucleation ,biology.organism_classification ,Catalysis ,Inorganic Chemistry ,Molecular Weight ,Crystallography ,Apoferritins ,biology.protein ,Tetra ,Ceruloplasmin ,Biomineralization - Abstract
Human cytoplasmic ferritins are heteropolymers of H and L subunits containing a catalytic ferroxidase center and a nucleation site for iron biomineralization, respectively. Here, ESI-MS successfully detected labile metal–protein interactions revealing the formation of tetra- and octa-iron clusters bound to L subunits, as previously underscored by X-ray crystallography.
- Published
- 2021
39. Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
- Author
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Giarita Ferraro, Francesca Sacco, Antonello Merlino, Lara Massai, Giorgio Facchetti, Matteo Tarchi, Isabella Rimoldi, Luigi Messori, Sacco, F., Tarchi, M., Ferraro, G., Merlino, A., Facchetti, G., Rimoldi, I., Messori, L., and Massai, L.
- Subjects
Models, Molecular ,Horse ,Crystallography, X-Ray ,Ligands ,Antineoplastic Agent ,Coordination Complexes ,Biology (General) ,Spectroscopy ,mass spectrometry ,biology ,Coordination Complexe ,Crystallography ,Mass spectrometry ,Platinum complexes ,Cytochrome c ,Cytochromes c ,General Medicine ,Human serum albumin ,Computer Science Applications ,Chemistry ,medicine.drug ,Human ,Protein Binding ,Platinum complexe ,Spectrometry, Mass, Electrospray Ionization ,RNase P ,Stereochemistry ,Protein Domain ,QH301-705.5 ,chemistry.chemical_element ,Ligand ,Antineoplastic Agents ,Bovine pancreatic ribonuclease ,Catalysis ,Article ,Adduct ,Inorganic Chemistry ,Protein Domains ,medicine ,Animals ,Humans ,Reactivity (chemistry) ,Horses ,Physical and Theoretical Chemistry ,Binding site ,crystallography ,Molecular Biology ,QD1-999 ,Platinum ,Binding Sites ,Animal ,Organic Chemistry ,Binding Site ,Ribonuclease, Pancreatic ,chemistry ,biology.protein ,Cattle ,Muramidase ,platinum complexes - Abstract
Three novel platinum(II) complexes bearing N-heterocyclic ligands, i.e., Pt2c, Pt-IV and Pt-VIII, were previously prepared and characterized. They manifested promising in vitro anticancer properties associated with non-conventional modes of action. To gain further mechanistic insight, we have explored here the reactions of these Pt compounds with a few model proteins, i.e., hen egg white lysozyme (HEWL), bovine pancreatic ribonuclease (RNase A), horse heart cytochrome c (Cyt-c) and human serum albumin (HSA), primarily through ESI MS analysis. Characteristic and variegate patterns of reactivity were highlighted in the various cases that appear to depend both on the nature of the Pt complex and of the interacting protein. The protein-bound Pt fragments were identified. In the case of the complex Pt2c, the adducts formed upon reaction with HEWL and RNase A were further characterized by solving the respective crystal structures: this allowed us to determine the exact location of the various Pt binding sites. The implications of the obtained results are discussed in relation to the possible mechanisms of action of these innovative anticancer Pt complexes.
- Published
- 2021
40. Au
- Author
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Giulia, Gorini, Francesca, Magherini, Tania, Fiaschi, Lara, Massai, Matteo, Becatti, Alessandra, Modesti, Luigi, Messori, and Tania, Gamberi
- Subjects
mitochondria ,gold(III)-based compounds ,apoptosis signal pathway ,thioredoxin reductase ,Article ,A2780 ovarian cancer cells - Abstract
Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in vitro toward a large number of human cancer cell lines. To expand the knowledge on the molecular mechanisms through which these gold(III) complexes trigger apoptosis in cancer cells, further studies have been performed using A2780 ovarian cancer cells as reference models. For comparative purposes, parallel studies were carried out on the gold(III) complex AuL12 (dibromo(ethylsarcosinedithiocarbamate)gold(III)), whose proapoptotic profile had been earlier characterized in several cancer cell lines. Our results pointed out that all these gold(III) compounds manifest a significant degree of similarity in their cellular and proapoptotic effects; the main observed perturbations consist of potent thioredoxin reductase inhibition, disruption of the cell redox balance, impairment of the mitochondrial membrane potential, and induction of associated metabolic changes. In addition, evidence was gained of the remarkable contribution of ASK1 (apoptosis-signal-regulating kinase-1) and AKT pathways to gold(III)-induced apoptotic signaling. Overall, the observed effects may be traced back to gold(III) reduction and subsequent formation and release of gold(I) species that are able to bind and inhibit several enzymes responsible for the intracellular redox homeostasis, in particular the selenoenzyme thioredoxin reductase.
- Published
- 2021
41. Cyclodextrin Inclusion Complexes of Auranofin and Its Iodido Analog: A Chemical and Biological Study
- Author
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Francesca Maestrelli, Ida Landini, Damiano Cirri, Enrico Mini, Lara Massai, and Luigi Messori
- Subjects
chemistry.chemical_classification ,Auranofin ,cyclodextrin encapsulation ,Cyclodextrin ,010405 organic chemistry ,Chemistry ,Communication ,auranofin ,Pharmaceutical Science ,Biological activity ,010402 general chemistry ,metal-based drugs ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Adduct ,RS1-441 ,Pharmacy and materia medica ,Gold Compounds ,Stability constants of complexes ,In vivo ,medicine ,Solubility ,medicine.drug - Abstract
Auranofin (AF) and its iodido analog, i.e., Au(PEt3) I (AFI), were reported to exhibit very promising anticancer properties both in vitro and in vivo. However, both these gold compounds have a scarce aqueous solubility that hampers their pharmaceutical use. Here, we explore whether encapsulation of these metallodrugs inside hydroxypropyl-beta–cyclodextrin (HPβ–CD) may lead to an improved biopharmaceutical profile for the resulting adducts. Phase solubility studies, performed at 25 °C in an aqueous buffer, revealed, in both cases, the formation of a 1:1 drug to cyclodextrin complex; a far greater apparent stability constant (K1:1) was measured for AFI compared to AF (331 M−1 versus ca. 30 M−1). NMR studies conducted on the AFI/HPβ–CD system confirmed the formation of a stable 1:1 adduct. Then, binary systems of AF and AFI with HPβ–CD were prepared by colyophilization and characterized by DSC and PXRD. The results revealed the occurrence of drug complexation and/or amorphization for the AFI/HPβ–CD binary system. Afterwards, the antiproliferative properties of the two cyclodextrin adducts and of the corresponding free drugs were comparatively evaluated in vitro in three representative ovarian cancer cell lines, i.e., A2780, SKOV3, and IGROV-1. The results, in all cases, point out that CD complexation of the two gold drugs does not substantially affect their biological activity. The implications of these findings are discussed in the frame of the current knowledge of AF and its analogs.
- Published
- 2021
42. Leaf Decoction of Carica papaya Combined with Artesunate Prevents Recrudescence in Plasmodium berghei-Infected Mice
- Author
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Anna Rosa Sannella, Anastasia Karioti, Stefania Orsini, Aldo Scalone, Luigi Gradoni, Luigi Messori, Carlo Severini, and Anna Rita Bilia
- Subjects
Pharmacology ,Mice, Inbred BALB C ,Carica ,Plasmodium berghei ,Organic Chemistry ,Artesunate ,Pharmaceutical Science ,Malaria ,Analytical Chemistry ,Plant Leaves ,Antimalarials ,Mice ,Complementary and alternative medicine ,Recurrence ,parasitic diseases ,Drug Discovery ,Animals ,Molecular Medicine ,Drug Therapy, Combination ,Female ,Plant Preparations ,Chromatography, High Pressure Liquid ,Phytotherapy - Abstract
Malaria treatment and control have become increasingly difficult because of the spread of drug-resistant strains of Plasmodium falciparum and Plasmodium vivax. Thus, there is a continuous need to develop new combination therapies such as artemisinin-based combination therapies (ACTs) to contrast the emergence of resistant Plasmodium strains. Despite ACT has been recommended by the World Health Organization since 2001, its overall deployment in poor endemic areas is very slow, principally due to its high cost. In the malaria endemic areas, plant remedies are still widely used mostly without assurance of their efficacy and/or safety. A variety of widespread herbal drugs or natural products were already reported for their possible plasmodicidal activities, but the studies concerning their activity in combination with artemisinins are very scarce. The antimalarial activity of papaya is mostly anecdotal, and the present study is aimed at investigating the antiplasmodial activity of a decoction obtained by traditional recipe from the mature leaves of Carica papaya. The decoction was analyzed by HPLC-DAD-MS (high performance liquid chromatography coupled with diodoarray detector and mass spectrometry) showing the presence of caffeoyl derivatives and di- and triglycosides of flavonols. The extract was found to be active against P. falciparum 3D7 strains with a synergism in the presence of artemisinin. In vivo activity against the murine malaria model of Plasmodium berghei was disclosed both for the dried extract alone (250, 500, and 750 mg/kg/d) and for its combination with artesunate (250 mg/kg/d papaya plus 10 mg/kg/d artesunate). This combination displayed the greatest antimalarial activity in terms of reduction of parasitemia and prevention of recrudescence in animals recovered from the infection.
- Published
- 2019
43. Induction of a Four‐Way Junction Structure in the DNA Palindromic Hexanucleotide 5′‐d(CGTACG)‐3′ by a Mononuclear Platinum Complex
- Author
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Bianka Siewert, Samantha L. Hopkins, Maxime A. Siegler, Marta Ferraroni, Luigi Messori, Paola Gratteri, Anja Busemann, Francesco Papi, Corjan van de Griend, Mathijs F. Wissingh, Sylvestre Bonnet, Carla Bazzicalupi, Vincent H. S. van Rixel, and Tiziano Marzo
- Subjects
Models, Molecular ,Stereochemistry ,Stacking ,Supramolecular chemistry ,chemistry.chemical_element ,Crystal structure ,010402 general chemistry ,01 natural sciences ,Oligomer ,Catalysis ,supramolecular chemistry ,Adduct ,chemistry.chemical_compound ,DNA Superstructures ,Humans ,platinum ,010405 organic chemistry ,Hydrogen bond ,Communication ,General Medicine ,General Chemistry ,DNA ,hydrogen bonding ,Communications ,hydrogen bonding · metallodrugs · nucleic acids ·platinum · supramolecular chemistry ,0104 chemical sciences ,nucleic acids ,chemistry ,metallodrugs ,Nucleic Acid Conformation ,Platinum - Abstract
Four‐way junctions (4WJs) are supramolecular DNA assemblies comprising four interacting DNA strands that in biology are involved in DNA‐damage repair. In this study, a new mononuclear platinum(II) complex 1 was prepared that is capable of driving the crystallization of the DNA oligomer 5′‐d(CGTACG)‐3′ specifically into a 4WJ‐like motif. In the crystal structure of the 1–CGTACG adduct, the distorted‐square‐planar platinum complex binds to the core of the 4WJ‐like motif through π–π stacking and hydrogen bonding, without forming any platinum–nitrogen coordination bonds. Our observations suggest that the specific molecular properties of the metal complex are crucially responsible for triggering the selective assembly of this peculiar DNA superstructure.
- Published
- 2019
44. Reactivity of CORM [RuII(CO)3Cl2{N-(N1-methylbenzimidazole)}] with aminoacids. Synthesis, and analytical and structural study for the new binuclear cis-[RuI(CO)2(N-MBI)(μ2-O,O-BAL)]2 sawhorse complex at solid state and in solution
- Author
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Gabriella Tamasi, Marco Consumi, Alessandro Donati, Claudio Rossi, Renzo Cini, Luigi Messori, Agnese Magnani, Gemma Leone, and Claudia Bonechi
- Subjects
010405 organic chemistry ,Chemistry ,Ligand ,Dimer ,Organic Chemistry ,Cationic polymerization ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,Ruthenium ,Inorganic Chemistry ,Crystallography ,chemistry.chemical_compound ,Oxidation state ,X-ray crystallography ,Molecule ,Reactivity (chemistry) ,Spectroscopy - Abstract
The reaction of fac-[RuII(CO)3Cl2( N 3-MBI)], 1, (MBI = N1-methylbenzimidazole) with HBAL (HBAL, N-benzoyl- dl -alanine) brought about cis-[RuI(CO)2( N 3-MBI)(μ2- O , O -BAL)]2, 2. The new binuclear organometallic compound was structurally characterized via X-ray diffraction (XRD, 293 ± 1 K) and FT-IR (KBr matrix) at the solid state, and via 1H-NMR (1·10−2 M, CDCl3) and UV-Vis (8.6·10−5 M, CH3OH) in solution. Simulation of the molecular structure was carried out at DFT-B3LYP/(Ru, Lanl2DZ; CHNO, 6-31G**) level at the gas phase, and structural parameters were compared to experimental (XRD) parameters for 2, and equivalent computations previously performed for the parent mononuclear RuII complex, 1. The absence of any other anionic/cationic molecule either as ligand or co-crystallized species, in addition to the two bridging carboxylato molecules per each dimer molecule was in agreement with the (+1) oxidation state for the two ruthenium centers. The two MBI ligands resulted linked to the metal atoms in trans position with respect to the Ru Ru bond. The Ru Ru, and the Ru N vectors measure 2.6984(4), and 2.236(4) and 2.183(4) A, respectively.
- Published
- 2019
45. Arsenoplatin-1 Is a Dual Pharmacophore Anticancer Agent
- Author
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Tiziano Marzo, Andrew P. Mazar, Giarita Ferraro, Richard W. Ahn, Luigi Messori, Sara Abuhadba, Đenana Miodragović, Thomas V. O'Halloran, Antonello Merlino, Abraham Bogachkov, Elden P. Swindell, Miodragovic, D., Merlino, A., Swindell, E. P., Bogachkov, A., Ahn, R. W., Abuhadba, S., Ferraro, G., Marzo, T., Mazar, A. P., Messori, L., and O'Halloran, T. V.
- Subjects
Organoplatinum Compounds ,cisplatin ,Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Article ,Catalysis ,Structure-Activity Relationship ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Arsenic Trioxide ,Cell Line, Tumor ,protein metalation, cancer research, metallodrugs ,Hydrolase ,Arsenoplatin ,Arsenous acid ,medicine ,Humans ,cancer ,Structure–activity relationship ,Arsenic trioxide ,Cell Proliferation ,Cisplatin ,Dose-Response Relationship, Drug ,Molecular Structure ,General Chemistry ,AP-1 ,Combinatorial chemistry ,0104 chemical sciences ,anticancer drugs ,Arsenoplatin, AP-1, cancer, anticancer drugs, cisplatin, trisenox, NCI-60 ,trisenox ,chemistry ,Cell culture ,Drug Screening Assays, Antitumor ,Pharmacophore ,DNA ,NCI-60 ,medicine.drug - Abstract
Arsenoplatins are adducts of two chemically important anticancer drugs, cisplatin and arsenic trioxide, that have a Pt(II) bond to an As(III) hydroxide center. Screens of the NCI-60 human tumor cell lines reveal that arsenoplatin-1 (AP1), [Pt(μ-NHC(CH(3))O)(2)ClAs(OH)(2)], the first representative of this novel class of anti-cancer agents, displays a superior activity profile relative to the parent drugs As(2)O(3) or cisplatin in majority of cancer cell lines tested. These activity profiles are important because the success of arsenic trioxide in blood cancers (such as APL) has not been seen in solid tumors due to the rapid clearance of arsenous acid from the body. To understand the biological chemistry of these compounds, we evaluated interactions of AP-1 with the two important classes of biomolecules – proteins and DNA. The first structural studies of AP-1 bound to model proteins reveal that platinum(II) binds the Nε of His in a manner that preserves the Pt-As bond. We find that AP-1 readily enters cells and binds to DNA with an intact Pt-As bond (Pt:As ratio of 1). At longer incubation times, however, the Pt:As ratio in DNA samples increases, suggesting that the Pt-As bond breaks and releases the As(OH)(2) moiety. We conclude that arsenoplatin-1 has the potential to deliver both Pt and As species to a variety of hematological and solid cancers.
- Published
- 2019
46. Platinum-based Anticancer Drugs: Unveiling Novel Mechanisms of Action of Conventional Metallodrugs for Improved Therapies
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Tiziano Marzo, Luigi Messori, and Diego La Mendola
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Action (philosophy) ,chemistry ,Coordination Complexes ,business.industry ,Drug Discovery ,Medicine ,chemistry.chemical_element ,Antineoplastic Agents ,General Medicine ,Pharmacology ,business ,Platinum - Published
- 2021
47. Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA–PEG nanoparticles
- Author
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Tiziano Marzo, Alessio Menconi, Damiano Cirri, Alessandro Pratesi, Mirko Severi, Lorenzo Antonuzzo, Lara Massai, Giulia Petroni, Luigi Messori, and Serena Pillozzi
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Auranofin ,Cell Survival ,Polyesters ,Antineoplastic Agents ,Capsules ,010402 general chemistry ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Article ,Polyethylene Glycols ,Biomaterials ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Tumor Cells, Cultured ,Cytotoxic T cell ,Humans ,Protein kinase B ,PLGA–PEG nanoparticles ,Cell Proliferation ,Chemistry ,Autophagy ,Cell Cycle ,Metals and Alloys ,Anticancer complexes ,Colorectal cancer ,In vitro ,0104 chemical sciences ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Nanoparticles ,Signal transduction ,Drug Screening Assays, Antitumor ,General Agricultural and Biological Sciences ,Colorectal Neoplasms ,Organogold Compounds ,medicine.drug - Abstract
Chloro(triethylphosphine)gold(I), (Et3PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et3PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et3PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et3PAuCl was encapsulated in biocompatible PLGA–PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et3PAuCl (nano-Et3PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et3PAuCl, was clearly documented. The implications of these findings are discussed.
- Published
- 2021
48. Ruthenium(II) 1,4,7-trithiacyclononane complexes of curcumin and bisdemethoxycurcumin: Synthesis, characterization, and biological activity
- Author
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Fenghe Duan, Diego La Mendola, Alessia Tombesi, Chiara Giacomelli, Gabriele Balducci, Luigi Messori, Laura Marchetti, Tiziano Marzo, Riccardo Pettinari, Fabio Marchetti, Enzo Alessio, Liming Zhou, Maria Letizia Trincavelli, Pettinari, Riccardo, Marchetti, Fabio, Tombesi, Alessia, Duan, Fenghe, Zhou, Liming, Messori, Luigi, Giacomelli, Chiara, Marchetti, Laura, Trincavelli, Maria Letizia, Marzo, Tiziano, La Mendola, Diego, Balducci, Gabriele, and Alessio, Enzo
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Models, Molecular ,Curcumin ,Ruthenium complexes ,Cell Survival ,Metal complexes interaction with protein lysozyme ,chemistry.chemical_element ,Antineoplastic Agents ,010402 general chemistry ,Crystallography, X-Ray ,Bisdemethoxycurcumin ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Ruthenium ,Anticancer activity ,Inorganic Chemistry ,chemistry.chemical_compound ,7-trithiacyclononane ,1,4,7-trithiacyclononane ,1,4,7-Trithiacyclononane ,Coordination Complexes ,Neoplasms ,Alkanes ,Tumor Cells, Cultured ,Humans ,Reactivity (chemistry) ,Sulfur Compounds ,010405 organic chemistry ,Ruthenium complexe ,Cationic polymerization ,Bioinorganic chemistry ,Biological activity ,0104 chemical sciences ,chemistry ,Lysozyme - Abstract
Two cationic ruthenium(II) 1,4,7-trithiacyclononane ([9]aneS3) complexes of curcumin (curcH) and bisdemethoxycurcumin (bdcurcH), namely [Ru(curc)(dmso-S)([9]aneS3)]Cl (1) and [Ru(bdcurc)(dmso-S)([9]aneS3)]Cl (2) were prepared from the [RuCl2(dmso-S)([9]-aneS3)] precursor and structurally characterized, both in solution and in the solid state by X-ray crystallography. The corresponding PTA complexes [Ru(curc)(PTA)([9]aneS3)]Cl (3) and [Ru(bdcurc)(PTA)([9]aneS3)]Cl (4) have been also synthesized and characterized (PTA = 1,3,5-triaza-7-phosphaadamantane). Bioinorganic studies relying on mass spectrometry were performed on complexes 1–4 to assess their interactions with the model protein lysozyme. Overall, a rather limited reactivity with lysozyme was highlighted accompanied by a modest cytotoxic potency against three representative cancer cell lines. The moderate pharmacological activity is likely connected to the relatively high stability of these complexes.
- Published
- 2021
49. On the Different Mode of Action of Au(I)/Ag(I)-NHC Bis-Anthracenyl Complexes Towards Selected Target Biomolecules
- Author
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Tiziano Marzo, Luigi Messori, Chiara Gabbiani, Federica Guarra, Tarita Biver, Damiano Cirri, Alessandro Pratesi, and Francesca Binacchi
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Silver ,gold carbene ,Macromolecular Substances ,Intercalation (chemistry) ,Pharmaceutical Science ,Nucleic Acid Denaturation ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,Silver chloride ,chemistry.chemical_compound ,Structure-Activity Relationship ,Gold Compounds ,lcsh:Organic chemistry ,mode of action ,Heterocyclic Compounds ,Drug Discovery ,Physical and Theoretical Chemistry ,Bovine serum albumin ,quadruplexes ,biology ,Molecular Structure ,Chemistry ,Spectrum Analysis ,Organic Chemistry ,Serum Albumin, Bovine ,DNA ,Models, Theoretical ,Fluorescence ,silver carbene ,Crystallography ,nucleic acids ,Chemistry (miscellaneous) ,Polynucleotide ,Covalent bond ,biology.protein ,target selectivity ,Molecular Medicine ,RNA ,Thermodynamics ,Gold ,Selectivity ,Methane ,protein metalation ,Algorithms - Abstract
Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multiple techniques are here used to unveil the mechanistic details of the binding to different biosubstrates of bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride [Ag(EIA)2]Cl and bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) gold chloride [Au(EIA)2]Cl. As the biosubstrates, we tested natural double-stranded DNA, synthetic RNA polynucleotides (single-poly(A), double-poly(A)poly(U) and triple-stranded poly(A)2poly(U)), DNA G-quadruplex structures (G4s), and bovine serum albumin (BSA) protein. Absorbance and fluorescence titrations, mass spectrometry together with melting and viscometry tests show significant differences in the binding features between silver and gold compounds. [Au(EIA)2]Cl covalently binds BSA. It is here evidenced that the selectivity is high: low affinity and external binding for all polynucleotides and G4s are found. Conversely, in the case of [Ag(EIA)2]Cl, the binding to BSA is weak and relies on electrostatic interactions. [Ag(EIA)2]Cl strongly/selectively interacts only with double strands by a mechanism where intercalation plays the major role, but groove binding is also operative. The absence of an interaction with triplexes indicates the major role played by the geometrical constraints to drive the binding mode.
- Published
- 2020
- Full Text
- View/download PDF
50. Ferritin-based anticancer metallodrug delivery: Encapsulation of Arsenoplatin-1 within the ferritin nanocage
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Paola Imbimbo, Giarita Ferraro, Luigi Messori, Denana Miodragovic, Alessandro Pratesi, Antonello Merlino, Thomas O' Halloran, and Daria Maria Monti
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Ferritin ,Nanocages ,biology ,Chemistry ,biology.protein ,Nanotechnology ,Encapsulation (networking) - Published
- 2020
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