DNA and BSA Interaction Studies and Antileukemic Evaluation of Polyaromatic Thiosemicarbazones and Their Copper Complexes

Some ten million cancer deaths occurred in 2020, highlighting the fact that the search for new anticancer drugs remains extremely topical. In the search for new coordination compounds with relevant biological properties, the choice of a metal ion is important for the design of the complex. In this regard, copper plays a peculiar role, thanks to its distinct properties. Thiosemicarbazones are, analogously, a unique class of ligands because they are easily modifiable, and therefore, extremely versatile in terms of modulating molecular properties. In this work, we synthesized and characterized, by means of X-ray diffraction, four new naphthaldehyde and anthraldehyde thiosemicarbazone derivatives and their copper complexes to be used in interaction studies with biological systems. The objective was to evaluate the antileukemic activity of these compounds. Reactions of these ligands with Cu(II) salts produced unexpected oxidation products and the isolation of Cu(I) metal complexes. One ligand and its related Cu(I) complex, which is stable in physiological conditions, were subjected to in vitro biological tests (UV-Vis and CD titration). An important interaction with DNA and an affinity toward BSA were observed in FT-IR experiments. Preliminary in vitro biological tests against a histiocytic lymphoma cell line revealed an interestingly low IC50 value, i.e., 5.46 µM, for the Cu(I) comple

Tris(1,2-diamino­ethane)­nickel(II) hexa­fluoridosilicate

The ionic title complex, [Ni(C2H8N2)3](SiF6), is built up of [Ni(en)3]2+ complex cations (en = 1,2-diamino­ethane) and hexa­fluoridosilicate anions. Single crystals of the title complex were isolated from an aqueous–ethano­lic Ni2+–en–SiF6 2− system. The Ni(II) and Si atoms are each located on a special position with site symmetry 3.2. The Ni(II) atom coordination sphere is octa­hedrally deformed, being coordinated by three chelating diamine ligands with an Ni—N distance of 2.1233 (18) Å. The crystal packing of the respective ions corresponds to the structure type of the hexa­gonal form of BN. Beside ionic forces, the packing is governed by N—H⋯F hydrogen bonds, which lead to the formation of hydro­phobic channels running along the 63 screw axis. The structure was refined as an inversion twin [0.49 (3): 0.51 (3)]

A New Photoactivatable Ruthenium(II) Complex with an Asymmetric Bis-Thiocarbohydrazone: Chemical and Biological Investigations

The synthesis, photoactivation and biological activity of a new piano-stool Ru(II) complex is herein reported. The peculiarity of this complex is that its monodentate ligand which undergoes the photodissociation is an asymmetric bis-thiocarbohydrazone ligand that possesses a pyridine moiety binding to Ru(II) and the other moiety contains a quinoline that endows the ligand with the capacity of chelating other metal ions. In this way, upon dissociation, the ligand can be released in the form of a metal complex. In this article, the double ability of this new Ru(II) complex to photorelease the ligand and to chelate copper and nickel is explored and confirmed. The biological activity of this compound is studied in cell line A549 revealing that, after irradiation, proliferation inhibition is reached at very low half maximal inhibitory concentration (IC50) values. Further, biological assays reveal that the dinuclear complex containing Ni is internalized in cells

Chromosome 3p alterations in pancreatic endocrine neoplasia

Pancreatic endocrine tumors (PET) are rare neoplasms classified as functioning (F-PET) or non-functioning (NF-PET) according to the presence of a clinical syndrome due to hormonal hypersecretion. PETs show variable degrees of clinical aggressiveness and loss of chromosome 3p has been suggested to be associated with an advanced stage of disease. We assessed chromosome 3p copy number in 113 primary PETs and 32 metastases by fluorescence in situ hybridization (FISH) using tissue microarrays. The series included 56 well-differentiated endocrine tumors (WDET), 62 well-differentiated endocrine carcinomas (WDEC), and 6 poorly differentiated endocrine carcinomas (PDEC). Chromosome 3p alterations were found in 23/113 (20%) primary tumors, with losses being predominant over gains (14% vs. 6%). Loss of 3p was found in 5/55 (9%) WDET, 11/52 (21%) WDEC, and never in PDEC. Gains of 3p were detected in 4/55 (7%) WDET, no WDEC, but notably in 3/6 (50%) PDEC (OR 23.6; P = 0.003). Metastases were more frequently monosomic for 3p compared to primary tumors (OR 3.6; P = 0.005). Monosomy was significantly associated with larger tumor size, more advanced tumor stage, and metastasis. No association was found with survival. Chromosome 3p copy number alterations are frequent events in advanced stage PET, with gains prevailing in PDEC while losses are more frequent in WDEC, supporting the view that a specific pattern of alterations are involved in these diverse disease subtypes

Antiproliferative activity of a series of cisplatin-based Pt(IV)-acetylamido/carboxylato prodrugs

We report studies of a novel series of Pt(IV) complexes exhibiting an asymmetric combination of acetylamido and carboxylato ligands in the axial positions. We demonstrate efficient synthesis of a series of analogues, differing in alkyl chain length and hence lipophilicity, from a stable acetylamido/hydroxido complex formed by reaction of cisplatin with peroxyacetimidic acid (PAIA). NMR spectroscopy and X-ray crystallography confirm the identity of the resulting complexes, and highlight subtle differences in structure and stability of acetylamido complexes compared to equivalent acetato complexes. Reduction of acetylamido complexes, whether achieved chemically or electro-chemically, is significantly more difficult than of acetate complexes, resulting in lower antiproliferative activity for shorter-chain complexes. For those with longer chains and hence greater cell uptake, this difference is negated and acetylamido complexes are as active as acetato analogues, both exhibiting antiproliferative potency (1/IC50) against A2780 ovarian cancer cells similar to that of cisplatin