Structure and Cytotoxic Properties of Some Selected Gold(III) Complexes

We prepared four representative square planar gold(III) complexes - [AuCl3(Hpm)], [AuCl2(esal)], [AuCl(dien)]Cl2 and [Au(en)2]Cl3 -and characterized them both in the solid state and in solution. Thereafter, the cytotoxicity of these compounds was evaluated in vitro against the A2780 human ovarian tumor cell line that was used as the reference cell line. Remarkably, ali these gold(III) complexes showed significant cytotoxic effects, [AuCl2(esal)] showing a potency comparable to cisplatin. The present gold(III) complexes were also tested on the corresponding cisplatin-resistant line and revealed they were able to overcome resistance to cisplatin to a large extent. The implications of these findings for the development of new gold(III) complexes to be tested as antitumor agents are discussed

Dinuclear gold(III) complexes as potential anticancer agents: structure, reactivity and biological profile of a series of gold(III) oxo-bridged derivatives

Six homologous gold(III) dinuclear oxo-bridged complexes, of the type [(bipynR)Au(μ-O)2Au(bipynR)][PF6]2, bearing variously substituted 2,2'-bipyridine ligands (bipynR = 2,2'-bipyridine, 4,4'-di-tert-butyl-, 6-methyl-, 6-neopentyl-, 6-o-xylyl- and 6,6'-dimethyl-2,2'-bipyridine), here called Auoxos, were prepared, characterised and recently tested as potential anticancer agents. Crystal structures were obtained for five members of the series that allowed us to perform detailed comparative analyses. Interestingly, the various Auoxos showed an acceptable stability profile in buffer solution and turned out to manifest outstanding antitumor properties in vitro. In particular, one member of this family, Auoxo6 (bipynR = 6,6'-dimethyl-2,2'-bipyridine), produced more selective and far greater antiproliferative effects than all other tested Auoxos, qualifying itself as the best “drug candidate”. In turn, COMPARE analysis of the cytotoxicity profiles of five Auoxos, toward an established panel of thirty-six human tumor cell lines, revealed important mechanistic differences; a number of likely biomolecular targets could thus be proposed such as HDAC and PKC. Biophysical studies revealed markedly different modes of interaction with calf thymus DNA for two representative Auoxo compounds. In addition, a peculiar reactivity with model proteins was documented on the ground of spectrophotometric and ESI MS data, most likely as the result of redox processes. In view of the several experimental evidences gathered so far, it can be stated that Auoxos constitute a novel family of promising cytotoxic gold compounds with an innovative mechanism of action that merit a more extensive pharmacological evaluation

Synthesis, chemical characterization, and biological evaluation of a novel auranofin derivative as an anticancer agent

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 (i.e. human serum albumin and haemoglobin) and with a synthetic dodecapeptide reproducing the C-terminal portion of thioredoxin reductase were comparatively analyzed through 31P NMR and ESI-MS. Remarkable binding properties toward these biomolecules were disclosed. Moreover, the cytotoxic effects produced by AFETT on two ovarian cancer cell lines (A2780 and A2780 R) and one colorectal cancer cell line (HCT116) were analyzed and found to be strong and nearly superimposable to those of auranofin. Interestingly, for both compounds, the ability to induce downregulation of vimentin expression in A2780 R cells was evidenced. Despite its close similarity to auranofin, AFETT is reported to exhibit some peculiar and distinctive features such as a lower lipophilicity, an increased water solubility and a faster reactivity towards the selected target biomolecules. These differences might confer to AFETT significant pharmaceutical and therapeutic advantages over auranofin itself

Chlorido and bromido oxaliplatin analogues as potential agents for CRC treatment: Solution behavior, protein binding and cytotoxicity evaluation

Despite the widespread use of platinum drugs in the treatment of colorectal cancer (CRC), due to the heavy side effects and to intrinsic or acquired Pt resistance, new and more efficient drugs are urgently needed. Starting from the encouraging results obtained for the complex PtI2(DACH), we summarise here our recent advances, reporting data on the synthesis and the chemical and biological features of two oxaliplatin analogues i.e. PtBr2(DACH) and PtCl2(DACH). The comparative approach of these studies reveals how these analogues possess interesting and differential pharmacological properties as well as some peculiar features that may be conveniently exploited to shed light in the mechanistic aspects involved in the pharmacological action of the parent drug oxaliplatin. Furthermore, these findings may inspire the design of more effective Pt-based anticancer drugs to be used in CRC treatment

Surface X-ray Diffraction Study of a Bi-Layer Junction Based on Cu and Cd Sulfides for Photovoltaic Applications

none9noThis study investigates the crystal structure of thin films of chalcogenides, particularly a junction with a p-type (Cu2S) and an n-type (CdS) layer deposited one on top of the other on a Ag(111) substrate, starting from an aqueous solution and by means of electrochemical atomic layer deposition (E-ALD) (the system is denoted by (Cu2S)60/(CdS)60/Ag(111)).mixedTommaso Baroni; Francesco Di Benedetto; Andrea Giaccherini; Enrico Berretti; Francesca Russo; Annalisa Guerri; Massimo Innocenti; Francesco Carlà; Roberto FeliciBaroni, Tommaso; DI BENEDETTO, Francesco; Giaccherini, Andrea; Berretti, Enrico; Russo, Francesca; Guerri, Annalisa; Innocenti, Massimo; Carlà, Francesco; Felici, Robert

Operando SXRD study of the structure and growth process of Cu2S ultra-thin films

International audienceElectrochemical Atomic Layer Deposition (E-ALD) technique has demonstrated to be a suitable process for growing compound semiconductors, by alternating the under-potential deposition (UPD) of the metallic element with the UPD of the non-metallic element. The cycle can be repeated several times to build up films with sub-micrometric thickness. We show that it is possible to grow, by E-ALD, Cu2S ultra-thin films on Ag(111) with high structural quality. They show a well ordered layered crystal structure made on alternating pseudohexagonal layers in lower coordination. As reported in literature for minerals in the Cu-S compositional field, these are based on CuS3 triangular groups, with layers occupied by highly mobile Cu ions. This structural model is closely related to the one of the low chalcocite. The domain size of such films is more than 1000 angstrom in lateral size and extends with a high crystallinity in the vertical growth direction up to more than 10 nm. E-ALD process results in the growth of highly ordered and almost unstrained ultra-thin films. This growth can lead to the design of semiconductors with optimal transport proprieties by an appropriate doping of the intra metallic layer. The present study enables E-ALD as an efficient synthetic route for the growth of semiconducting heterostructures with tailored propertie

Pilot Investigation of SARS-CoV-2 Variants in the Island of Sicily Prior to and in the Second Wave of the COVID-19 Pandemic

8 páginas, 2 tablas, 2 figuras. The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/genbank/, OM510944; https://www.ncbi.nlm.nih.gov/genbank/, OM510945; https://www.ncbi. nlm.nih.gov/genbank/, OM510946; https://www.ncbi.nlm.nih. gov/genbank/, OM510947; https://www.ncbi.nlm.nih.gov/genbank/, OM510948; https://www.ncbi.nlm.nih.gov/genbank/, OM510949; https://www.ncbi.nlm.nih.gov/genbank/, OM51 0950; https://www.ncbi.nlm.nih.gov/genbank/, OM510951; and https://www.ncbi.nlm.nih.gov/genbank/, OM510952.After 2 years of the COVID-19 pandemic, we continue to face vital challenges stemming from SARS-CoV-2 variation, causing changes in disease transmission and severity, viral adaptation to animal hosts, and antibody/vaccine evasion. Since the monitoring, characterization, and cataloging of viral variants are important and the existing information on this was scant for Sicily, this pilot study explored viral variants circulation on this island before and in the growth phase of the second wave of COVID-19 (September and October 2020), and in the downslope of that wave (early December 2020) through sequence analysis of 54 SARS-CoV-2-positive samples. The samples were nasopharyngeal swabs collected from Sicilian residents by a state-run one-health surveillance laboratory in Palermo. Variant characterization was based on RT-PCR amplification and sequencing of four regions of the viral genome. The B.1.177 variant was the most prevalent one, strongly predominating before the second wave and also as the wave downsized, although its relative prevalence decreased as other viral variants, particularly B.1.160, contributed to virus circulation. The occurrence of the B.1.160 variant may have been driven by the spread of that variant in continental Europe and by the relaxation of travel restrictions in the summer of 2020. No novel variants were identified. As sequencing of the entire viral genome in Sicily for the period covered here was restricted to seven deposited viral genome sequences, our results shed some light on SARS-CoV-2 variant circulation during that wave in this insular region of Italy which combines its partial insular isolation with being a major entry point for the African immigration.This research received external funding to CR-G and EM from “Agencia Valenciana de Innovación: COVID-19, Ayudas de Concesión Directa a Soluciones Científico-Innovadoras Directamente Relacionadas Con La Lucha Contra La COVID-19,” (Ref COVID-19-203) and from “Conselleria de Innovación Universidades, Ciencia y Sociedad Digital: Subvenciones a Grupos de Investigación Emergentes” (Ref, GV/2021/163); to VR from the Agencia Estatal de Investigación of the Spanish Government (Ref PID2020-120322RB-C21) and from the European Commission–NextGeneration EU CSIC Global Health Platform, Spanish Ministry of Science and Innovation (Ref MCIN/AEI/10.13039/501100011033); and to the Istituto Zooprofilattico Sperimentale della Sicilia “A. Mirri” by the Project “COVID-19: Traiettorie Evolutive di SARS-CoV-2 ed Indagine Sul Ruolo Degli Animali” (IZS SI 03/20 RC), funded by the Italian Ministry of Health.Peer reviewe

A SARS-CoV-2 full genome sequence of the B.1.1 lineage sheds light on viral evolution in Sicily in late 2020

9 páginas, 2 figuras, 2 tablasTo investigate the influence of geographic constrains to mobility on SARS-CoV-2 circulation before the advent of vaccination, we recently characterized the occurrence in Sicily of viral lineages in the second pandemic wave (September to December 2020). Our data revealed wide prevalence of the then widespread through Europe B.1.177 variant, although some viral samples could not be classified with the limited Sanger sequencing tools used. A particularly interesting sample could not be fitted to a major variant then circulating in Europe and has been subjected here to full genome sequencing in an attempt to clarify its origin, lineage and relations with the seven full genome sequences deposited for that period in Sicily, hoping to provide clues on viral evolution. The obtained genome is unique (not present in databases). It hosts 20 single-base substitutions relative to the original Wuhan-Hu-1 sequence, 8 of them synonymous and the other 12 encoding 11 amino acid substitutions, all of them already reported one by one. They include four highly prevalent substitutions, NSP12:P323L, S:D614G, and N:R203K/G204R; the much less prevalent S:G181V, ORF3a:G49V and N:R209I changes; and the very rare mutations NSP3:L761I, NSP6:S106F, NSP8:S41F and NSP14:Y447H. GISAID labeled this genome as B.1.1 lineage, a lineage that appeared early on in the pandemic. Phylogenetic analysis also confirmed this lineage diagnosis. Comparison with the seven genome sequences deposited in late 2020 from Sicily revealed branching leading to B.1.177 in one branch and to Alpha in the other branch, and suggested a local origin for the S:G118V mutation.This research received external funding to CR-G from Conselleria de Innovación Universidades, Ciencia y Sociedad Digital: Subvenciones a Grupos de Investigación Emergentes (Ref, GV/2021/163); to VR from the Agencia Estatal de Investigación of the Spanish Government (Ref PID2020-120322RB-C21) and the European Commission-NextGeneration EU CSIC Global Health Platform, Spanish Ministry of Science and Innovation (Ref MCIN/AEI/10.13039/501100011033); and to the Istituto Zooprofilattico Sperimentale della Sicilia A. Mirri by the Project COVID-19: Traiettorie Evolutive di SARS-CoV-2 ed Indagine Sul Ruolo Degli Animali (IZS SI 03/20 RC), funded by the Italian Ministry of HealthPeer reviewe

Sviluppo di complessi di oro (3.) come farmaci antitumorali

Dottorato di ricerca in scienze chimiche. Tutore P. OrioliConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal