Maddalena Corsini

Bio: Maddalena Corsini is an academic researcher from University of Padua. The author has contributed to research in topics: NAMI-A & Dithiocarbamate. The author has an hindex of 3, co-authored 3 publications receiving 402 citations. Previous affiliations of Maddalena Corsini include University of Cagliari.

Gold(III) dithiocarbamate derivatives for the treatment of cancer: solution chemistry, DNA binding, and hemolytic properties.

Abstract: Gold(III) compounds are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents. We report here on the solution and electrochemical properties, and the biological behavior of some gold(III) dithiocarbamate derivatives which have been recently proved to be one to 4 orders of magnitude more cytotoxic in vitro than the reference drug (cisplatin) and to be able to overcome to a large extent both intrinsic and acquired resistance to cisplatin itself. Their solution properties have been monitored in order to study their stability under physiological conditions; remarkably, they have shown to undergo complete hydrolysis within 1 h, the metal center remaining in the +3 oxidation state. Their DNA binding properties and ability in hemolyzing red blood cells have been also evaluated. These gold(III) complexes show high reactivity toward some biologically important isolated macromolecules, resulting in a dramatic inhibition of both DNA and RNA synthesis and inducing DNA lesions with a faster kinetics than cisplatin. Nevertheless, they also induce a strong and fast hemolytic effect (compared to cisplatin), suggesting that intracellular DNA might not represent their primary or exclusive biological target.

Structural characterization, solution studies, and DFT calculations on a series of binuclear gold(III) oxo complexes: relationships to biological properties

Abstract: A series of structurally related oxo-bridged binuclear gold(III) compounds, [Au2(μ-O)2(N^N)2](PF6)2, where N^N is 2,2′-bipyridine or a substituted 2,2′-bipyridine, have recently been shown to exhibit appreciable stability under physiological-like conditions and to manifest important antiproliferative effects toward selected human tumor cell lines (J. Med. Chem. 2006, 49, 5524). The crystal structures of four members of this series, namely, [Au2(μ-O)2(bipy)2](PF6)2, cis-[Au2(μ-O)2(6-Mebipy)2](PF6)2, trans-[Au2(μ-O)2(6-oXylbipy)2](PF6)2, and [Au2(μ-O)2(6,6′-Me2bipy)2](PF6)2, have been solved here and the respective structural parameters comparatively analyzed. Remarkably, all of the compounds contain a common structural motif consisting of a Au2O2 “diamond core” linked to two bipyridine ligands in a roughly planar arrangement. Interestingly, introduction of different kinds of alkyl or aryl substituents on the 6 (and 6′) position(s) of the bipyridine ligand leads to small structural changes that nonetheless greatly affect the reactivity of the metal centers. The chemical behavior of these compounds in solution has been studied in detail, focusing in particular on the electrochemical properties. Some initial correlations among the structural parameters, the chemical behavior in solution, and the known cytotoxic effects of these compounds are proposed. Notably, we have found that the 6,6′-dimethyl-2,2′-bipyridine derivative, which showed the largest structural deviations with respect to the model compound [Au2(μ-O)2(bipy)2](PF6)2, also had the highest oxidizing power, the least thermal stability, and the greatest cytotoxic activity. The positive correlation that exists between the oxidizing power and the antiproliferative effects seems to be of particular interest. Moreover, the electronic structures of these compounds were extensively analyzed using DFT methods, and the effects of the various substituents on reactivity were predicted; overall, very good agreement between theoretical expectations and experimental data was achieved. In turn, theoretical predictions offer interesting hints for the design of new, more active binuclear gold(III) compounds.

Activity of rat cytosolic thioredoxin reductase is strongly decreased by trans-[bis(2-amino-5- methylthiazole)tetrachlororuthenate(III)]: first report of relevant thioredoxin reductase inhibition for a ruthenium compound.

Abstract: A novel “Keppler type” ruthenium(III) compound trans-[bis(2-amino 5-methylthiazole)tetrachlororuthenate(III)] 1, of potential interest as an anticancer agent, was designed, synthesized, and characterized Its interactions with various proteins were analyzed, including the selenoenzyme thioredoxin reductase, an emerging target for anticancer metallodrugs The selective inhibition of the cytosolic form of this selenoenzyme was documented, this being the first report of significant thioredoxin reductase inhibition by a ruthenium compound

Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs

Abstract: The discovery of cisplatin's antitumor activity in 1969 prompted the search for novel metal-containing complexes as potential anticancer drugs. Among these novel complexes, metal N-heterocyclic carbene (NHC) complexes have recently gained considerable attention because they perfectly fit prerequisites for efficient drug design and fast optimization. Moreover, most of them have shown higher cytotoxicity than cisplatin. This review describes the advances that have been achieved in using transition metal (Ag, Au, Pt, Pd, Cu, Ni, and Ru) complexes containing NHC ligands as antitumor agents. Their modes of action at the cellular lever are further discussed. All these initial achievements clearly demonstrate the great potential of metal–NHC complexes as antitumor agents.

Non platinum metal complexes as anti-cancer drugs.

Abstract: The development of metal complexes with platinum central atoms such as cisplatin or carboplatin had an enormous impact on current cancer chemotherapy. However, the spectrum of cancers that can be treated with platinum agents is narrow and treatment efficacy suffers from side effects and resistance phenomena. These unresolved problems in platinum-based anti-cancer therapy have stimulated increased research efforts in the search for novel non platinum-containing metal species as cytostatic agents. Preclinical and clinical investigations showed that the development of new metal agents with modes of action different from cisplatin is possible. Thus, complexes with iron, cobalt, or gold central atoms have shown promising results in preclinical studies and compounds with titanium, ruthenium, or gallium central atoms have already been evaluated in phase I and phase II trials. This review covers some relevant examples of preclinical and clinical research on novel non platinum metal complexes.