Showing papers by "Vieri Fusi published in 2014"

Modulating the Sensor Response to Halide Using NBD-Based Azamacrocycles

Abstract: Ligand L (2,6-bis{[7-(7-nitrobenzo[1,2,5]oxadiazole-4-yl)-3,10-dimethyl-1,4,7,10-tetraazacyclododeca-1-yl]methyl}phenol) is a fluorescent sensor that is useful for detecting Cu(II), Zn(II), and Cd(II). Some of the complexes formed are able to sense the presence of halides in solution. L passes through the cellular membrane, becoming fluorescent inside cells. The H–1L– species is able to form dinuclear complexes with [M2H–1L]3+ stoichiometry with Cu(II), Zn(II), and Cd(II) ions, experiencing a CHEF effect upon metal coordination in an acetonitrile/water 95:5 (v/v) solution. In all three of the complexes investigated, the metal cations are coordinatively unsaturated and can therefore bind secondary ligands as anionic species. The crystal structure of [Cd2(H–1L)Cl2](ClO4)·4H2O is discussed. The Zn(II) complex behaves as an OFF–ON sensor for fluoride and chloride anions.

An aza-macrocycle containing maltolic side-arms (maltonis) as potential drug against human pediatric sarcomas

Abstract: Identification of new drugs against paediatric sarcomas represents an urgent clinical need that mainly relies on public investments due to the rarity of these diseases. In this paper we evaluated the in vitro and in vivo efficacy of a new maltol derived molecule (maltonis), belonging to the family of molecules named hydroxypyrones. Maltonis was screened for its ability to induce structural alteration of DNA molecules in comparison to another maltolic molecule (malten). In vitro antitumour efficacy was tested using a panel of sarcoma cell lines, representative of Ewing sarcoma, osteosarcoma and rhabdomyosarcoma, the three most common paediatric sarcomas, and in normal human mesenchymal primary cell cultures. In vivo efficacy was tested against TC-71 Ewing sarcoma xenografts. Maltonis, a soluble maltol-derived synthetic molecule, was able to alter the DNA structure, inhibit proliferation and induce apoptotic cell death in paediatric sarcoma cells, either sensitive or resistant to some conventional chemotherapeutic drugs, such as doxorubicin and cisplatin. In addition, maltonis was able to induce: i) p21, p15 and Gadd45a mRNA upregulation; ii) Bcl-2, survivin, CDK6 and CDK8 down-regulation; iii) formation of γ-H2AX nuclear foci; iv) cleavage of PARP and Caspase 3. Two independent in vivo experiments demonstrated the tolerability and efficacy of maltonis in the inhibition of tumour growth. Finally maltonis was not extruded by ABCB1, one of the major determinants of chemotherapy failure, nor appeared to be a substrate of the glutathione-related detoxification system. Considering that treatment of poorly responsive patients still suffers for the paucity of agents able to revert chemoresistance, maltonis may be considered for the future development of new therapeutic approaches for refractory metastatic patients.

A Preorganized Metalloreceptor for Alkaline Earth Ions Showing Calcium Versus Magnesium Selectivity in Water: Biological Activity of Selected Metal Complexes

Abstract: The N,N'-bis((3-hydroxy-4-pyron-2-yl)methyl)-N,N'- dimethylethylendiamine (Malten = L) forms the highly stable (CuH2L) species in water, in which the converging maltol oxygen atoms form an electron-rich area able to host hard metal ions. When considering the alkaline earth series (AE), the (Cu(H2L)) species binds all metal ions, with the excep- tion of Mg 2 + , exhibiting the relevant property to discrimi- nate Ca 2 + versus Mg 2 + at physiological pH 7.4; the binding of the AE metal is visible to the naked eye. The stability con- stant values of the trinuclear (AE{Cu(H2L)}2) 2 + species formed reach the maximum for Ca 2 + (log K = 7.7). Ca 2 + also forms a tetranuclear (Ca{Cu(H2L)})2 4 + species at a high Ca 2 + concentration. Tri- and tetranuclear calcium complexes show blue- and pink-colored crystals, respectively. (Cu(H2L)) is the most active species in inducing DNA alterations. The DNA damages are compatible with its hydrolytic cleavages.