Riccardo Bonsignore

Riccardo Bonsignore
Università degli Studi di Palermo | UNIPA

Medicinal and Bioinorganic Chemistry

About

41
Publications
5,994
Reads
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709
Citations
Citations since 2016
34 Research Items
667 Citations
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
Introduction
Riccardo Bonsignore currently works at TUM. Riccardo does research in Cancer Research, Inorganic Chemistry and Medicinal Chemistry. His current projects are 'DNA binding of small molecules.' and "Aquaporins: design of gold complexes as selective inhibitors".
Additional affiliations
June 2020 - present
Technische Universität München
Position
  • PDRA
May 2017 - July 2020
Cardiff University
Position
  • Fellow
February 2015 - April 2017
Università degli Studi di Palermo
Position
  • Research Assistant
Description
  • Developing new heterocycles to target DNA-G-quadruplexes
Education
January 2011 - December 2013
Università degli Studi di Palermo
Field of study
  • Chemical Sciences
September 2003 - July 2010
Università degli Studi di Palermo, Facoltà di Farmacia
Field of study

Publications

Publications (41)
Article
Full-text available
The binding modes and free‐energy landscape of two AuI/N‐heterocyclic carbene complexes interacting with G‐quadruplexes, namely a human telomeric (hTelo) and a promoter sequence (C‐KIT1), are studied here for the first time by metadynamics. The theoretical results are validated by FRET DNA melting assays and provide an accurate estimate of the abso...
Article
Full-text available
With the aim of exploiting the use of organometallic species for the efficient modification of proteins through C‐atom transfer, we report here on the gold‐mediated cysteine arylation via reductive elimination process occurring from the reaction of cyclometalated Au(III) C^N complexes with a zinc finger peptide (Cys2His2 type). Among the four selec...
Article
Experimental organometallic gold(I) compounds hold promise for anticancer therapy. This study reports the synthesis of two novel families of gold(I) complexes, including N1-substituted bis-N-heterocyclic carbene (NHCs) complexes of general formula [Au(N1-TBM)2]BF4 (N1-TBM = N1-substituted 9-methyltheobromin-8-ylidene) and mixed gold(I) NHC-alkynyl...
Article
Full-text available
In recent years, the reactivity of gold complexes was shown to extend well beyond p ‐activation and to holds promises to achieve selective cross‐couplings in several C–C and C–E (E = heteroatom) bond forming reactions. Here, with the aim of exploiting new organometallic species for cross‐coupling reactions, we report on the Au(III)‐mediated C(sp 2...
Article
Full-text available
With the aim of exploiting new organometallic species for cross‐coupling reactions, we report here on the Au(III)‐mediated Caryl–P bond formation occurring upon reaction of C^N cyclometalated Au(III) complexes with phosphines. The [Au(C^N)Cl2] complex 1 featuring the bidentate 2‐benzoylpyridine (CCON) scaffold was found to react with PTA (1,3,5‐tri...
Article
With the aim of designing new metallosupramolecular architectures for drug delivery, research has focused on porous 3-dimensional (3D)-metallacages able to encapsulate cytotoxic agents protecting them from metabolism while targeting them to cancer sites. Here, two self-assembled [Pd2L4]4+ cages (CG1 and CG2) featuring 3,5-bis(3-ethynylpyridine)phen...
Article
With the idea of exploiting metal templated C–S bond forming reactions to achieve modification of cysteines in bacterial proteins, a cyclometalated Au(III) compound was explored in a competitive chemoproteomic approach in S. aureus cell extracts. More than 100 ligandable cysteines were identified, of which more than 50% were not engaged by organic...
Preprint
Full-text available
With the idea of exploiting metal-templated reactions to achieve selective modification of cysteines in proteins for antibacterial applications, an organometallic cyclometalated Au(III) compound was explored in a competitive chemoproteomic approach based on the isoDTB-ABPP (isotopically labelled desthiobiotin azide-activity-based protein profiling)...
Article
The inhibition of glycerol permeation via human aquaporin-10 (hAQP10) by organometallic gold complexes has been studied by fluorescence stopped-flow spectroscopy, and its mechanism has been described using molecular modelling and atomistic simulations. The most effective hAQP10 inhibitors are cyclometalated Au(III) C^N compounds known to efficientl...
Article
Full-text available
Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them a...
Article
Full-text available
The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal‐based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N com...
Article
Full-text available
The involvement of non‐canonical DNA structures, as G‐quadruplex (G4) DNA, in cancer development and progression has set the pace towards the renaissance of DNA‐binding metal complexes. In this work, we report the DNA‐binding of three Ni(II), Cu(II), Zn(II) complexes of a salphen‐like N4‐donor ligand, bearing two imidazole groups condensed with a p...
Article
Full-text available
Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better understandi...
Article
A cationic AuI N‐heterocyclic carbene complex featuring caffeine‐based ligands has shown potent and selective anticancer effects in ovarian cancer cells. This organogold compound is remarkably stable in physiological conditions. Therefore, the observed therapeutic effects are mainly due to non‐covalent interactions of the gold compound with its pha...
Article
Full-text available
The Front Cover shows a pathway towards the utilization of gold‐based compounds to inhibit infections caused by Leishmania parasites. The compounds are tested in the amastigote, the clinically relevant form of the parasite infecting macrophages. Cover design by Karen Minori and Mariana Brioschi. More information can be found in the Communication by...
Article
Full-text available
The organometallic Au(I) bis-N-heterocyclic carbene complex [Au(9-methylcaffeine-8-ylidene)2]+ (AuTMX2) was previously shown to selectively and potently stabilise telomeric DNA G-quadruplex (G4) structures. This study sheds light into the molecular reactivity and mode of action of AuTMX2 in the cellular context using mass spectrometry-based methods...
Preprint
Full-text available
Background Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better...
Article
Full-text available
A series of mononuclear coordination or organometallic Au(I)/ Au(III) complexes ( 1‐9 ) have been comparatively studied for their antileishmanial activity against promastigotes and amastigotes, the clinically relevant parasite form, of L. amazonensis and L. braziliensis in vitro . One of the cationic Au(I) bis‐N‐heterocyclic carbenes ( 3 ) features...
Article
Full-text available
To gain more insight into the factors controlling the efficient cysteine arylation by cyclometalated Au(III) complexes, the reaction between selected gold compounds and different peptides was investigated by high‐resolution liquid chromatography electrospray ionization mass spectrometry (HR‐LC‐ESI‐MS). The deducted mechanisms of C–S cross‐coupling,...
Article
The ability to track drugs inside of cells and tumours has been highly valuable in cancer research and diagnosis. Metal complexes add attractive features to fluorescent drugs, such as targeting and specificity, solubility and uptake or photophysical properties. This review focuses on the latest fluorescent metal-based complexes, their cellular targ...
Article
The DNA-binding of two salphen-like metal complexes of nickel(II) (1) and zinc(II) (2) was investigated in different ionic strength solutions by absorption spectroscopy. The data analysis allowed us to obtain the values of their extrapolated DNA-binding constant in physiological conditions, with DNA-binding strength in the order Ni > Zn, and to giv...
Article
Full-text available
With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic AuI complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3‐dihydroimidazolylidene) were synthesized and characterized by 1H and 13C NMR and elemental analysis, and in some...
Article
Full-text available
The binding modes and free‐energy landscape of two AuI/N‐heterocyclic carbene complexes interacting with G‐quadruplexes, namely a human telomeric (hTelo) and a promoter sequence (C‐KIT1), are studied here for the first time by metadynamics. The theoretical results are validated by FRET DNA melting assays and provide an accurate estimate of the abso...
Article
We report here on the synthesis of a series of mono- and dinuclear gold(I) complexes exhibiting sulfonated bis(NHC) ligands and novel hydroxylated mono(NHC) Au(I) compounds, which were also examined for their biological activities. Initial cell viability assays show strong antiproliferative activities of the hydroxylated mono(NHC) gold compounds (8...
Article
The duplex and G-quadruplex DNA-binding of six nickel(II) and zinc(II) complexes of three salphen-like ligands (salphen = N,N′-bis-salicylidene-1,2-phenylenediaminato) was investigated by UV–visible absorption and circular dichroism spectroscopy. The results obtained, in particular the values of the DNA-binding constants, Kb, point out that the nic...
Article
The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled...
Article
DNA-binding investigations showed that two different derivatives endowed with pyrene and imidazolium moieties, 1 and 2, strongly bind both double-stranded DNA and telomeric sequences in G-quadruplex (G4) conformation. The values of the DNA-binding constants indicate that 1 and 2 show preferential affinity for G4-DNA, of about one and two orders of...
Article
Background: Alzheimer's disease (AD) is the most common form of dementia that seriously affects daily life. Even if AD pathogenesis is still subject of debate, it is generally accepted that cerebral cortex plaques formed by aggregated amyloid-β (Aβ) peptide can be considered a characteristic pathological hallmark. It is well known that metal ions...
Article
Background: The treatment and diagnosis of Alzheimer's Disease (AD) are two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibrillary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain...
Article
Novel nickel(II) (1) and zinc(II) (2) complexes of a Salen-like ligand, carrying a pyrimidine ring on the N,N′ bridge, were synthesized and characterized. Their interaction with duplex and G-quadruplex DNA was investigated in aqueous solution through UV–visible absorption, circular dichroism and viscometry measurements. The results obtained point o...
Article
Background: Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billion-dollar legal dama...
Article
The Peruvian Andes are one of the most productive areas for mining and therefore also one of the most exposed to these sources of pollution. This article reports the characterization of Polycyclic Aromatic Hydrocarbons (PAHs) in sediments of Cerro de Pasco area (Peru) located close to a large open-pit mine and, in recent years, several reports have...
Article
Full-text available
The affinity of three square-planar nickel(II) (1), copper(II) (2) and zinc(II) (3) Schiff-base complexes for wild-type human telomeric (h-Telo) and protooncogene c-myc G-quadruplex (G4) DNA was investigated by UV-visible absorption spectroscopy and circular dichroism. DNA-binding constants (Kb) were determined by spectrophotometric titrations for...
Article
New benzothieno[3,2-d]-1,2,3-triazines, together with precursors triazenylbenzo[b]thiophenes, were designed, synthesized and screened as anticancer agents. The structural features of these compounds prompted us to investigate their DNA binding capability through UV-vis absorption titrations, circular dichroism, and viscometry, pointing out the occu...
Article
New technologies and higher prices of raw materials have promoted the expansion of mining activity throughout the world; if not properly regulated, this activity can lead to contamination of the local and regional environment. The city of Cerro de Pasco is located close to a large open-pit mine and in recent years, several reports have provided evi...
Article
In efforts to find agents with improved biological activity against cancer cells, recent years have seen an increased interest in the study of small molecules able to bind the deoxyribonucleic acid (DNA) when it assumes secondary structures known as G-quadruplexes (G4s) preferring them over the B form. To date, several compounds reported in literat...
Article
Full-text available
We present a thorough characterization of the interaction of novel nickel(ii) (), copper(ii) () and zinc(ii) () Schiff base complexes with native calf thymus DNA (ct-DNA), in buffered aqueous solution at pH 7.5. UV-vis absorption, circular dichroism (CD) and viscometry titrations provided clear evidence of the intercalative mechanism of the three s...
Conference Paper
Full-text available
Nuovi composti di-e tri-organostagno(IV) stati sintetizzati e e caratterizzati per essere testati per la loro capacità di causare citotossicità contro linee cellulari tumorali. I complessi sono stati ottenuti per reazione degli idrossidi e/o degli ossidi di organostagno(IV) con N a -Boc-Ornitina (Boc-Orn) in metanolo a riflusso. I dati analitici so...

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Projects (5)
Project
DNA is a major biotarget of clinically used anticancer drugs, as well as of many cytotoxic and carcinogenic compounds. From a chemical point of view, the knowledge of the position and nature of the chemical bond, e.g. covalent or non-covalent, between the polynucleotide and small molecules might be of help in unravelling, at a molecular level, the mechanism by which they exhibit their biochemical properties. Our research interests in this field aim at understanding the details of the interactions of DNA with drugs or with novel synthesized metal compounds and the consequences on their structural and spectroscopic properties, using both experimental and computational approaches.