Autophagy and apoptosis: studies on the effects of bisthiosemicarbazone copper(II) complexes on p53 and p53-null tumour cell lines

A comparative study between two bisthiosemicarbazones, 2,3-butanedione bis(4,4-dimethyl-3-thiosemicarbazone) and 2,3-butanedione bis(2-methyl-3-thiosemicarbazone), and their copper(II) complexes is reported. The four compounds have been tested on leukemia cell line U937 and on adenocarcinoma cell line A549. The study includes cell viability, cell cycle, morphological changes, assessment of apoptosis, analysis of autophagy, measurement of reactive oxygen species (ROS) and of lipid peroxidation, protein determination, assessment of the expression of p53 and cellular uptake of metal complexes. Tests about the copper uptake under normoxic and hypoxic conditions were also carried out on solid tumour cell line A549. The four compounds under study elicit different effects on the two lines adopted as representatives of p53 and p53-null cells. The role of the metal is relevant and it is likely that the metal-mediated oxidative stress plays an essential role in the whole process. The mechanisms induced by these molecules differ not only as a function of cell line but also of dose. The responses include two distinct self-destructive processes, autophagy and apoptosis

Heterocyclic substituted thiosemicarbazones and their Cu(II) complexes: Synthesis, characterization and studies of substituents effects on coordination and DNA binding

By reacting thiosemicarbazides substituted on the aminic nitrogen with 5-formyluracil, several new 5-formyluracil thiosemicarbazones (H3ut) derivatives were synthesised and characterized. These ligands, treated with copper chloride and nitrate, afforded two different kinds of compounds. In the complexes derived from copper chloride the metal atom is pentacoordinated, being surrounded by the neutral ligand binding through SNO donor atoms and by two chlorines, while the nitrate derivatives consist of monocations and nitrate anions. The copper coordination (4 + 2) involves the SNO ligand atoms, two water oxygens and an oxygen atom of a monodentate nitrate group. On varying the substituents on the thiosemicarbazidic moiety, remarkable modifications of the coordination geometry are not observed for the complexes with the same counterion. For all the compounds, interactions with DNA (calf thymus) were studied using UV–Vis spectroscopy; the nuclease activity was verified on plasmid DNA pBR 322 by electrophoresis

Synthesis and characterization of 4-fluorobenzaldehyde thiosemicarbazone derivatives as corrosion inhibitors

In this paper, we report the syntheses, characterization and studies on the inhibition efficiency in mild steel acidic corrosion of 4-fluorobenzaldehyde thiosemicarbazone, Hfbt, 4-fluorobenzaldehyde 2-methylthiosemicarbazone, Me-fbt, and their Zn(II) complexes [Zn(fbt)2] and [Zn(Me-fbt)2]Cl2. The ligands present a good degree of activity that can be assigned to their molecular planar shape and to the presence of electron lone pairs that can interact with metal orbitals. The two zinc complexes present diametrically opposite properties: [Zn(fbt)2] is by far less active than the ligands, while [Zn(Me-fbt)2]Cl2 is the most efficient. Quantum chemical studies were carried out in an attempt to rationalize this behaviour