Beliefs and attitudes among Italian high school students toward people with severe mental disorders

The negative attitudes surrounding mental disorders and their treatment are a major obstacle to the correct identification and treatment of emerging psychopathologies. The purpose of this study was to investigate mental health literacy in a large and representative sample of high school students in Italy, via a booklet containing several questionnaires delivered to 1032 teenagers. The items in the questionnaires probed knowledge about mental health and illness, stigmatization, stereotypes, behaviors, opinions, and attitudes. In general, the students had a reasonable knowledge of mental disorders and were able to distinguish these from somatic disorders. However, a large portion of the students nourished some misconceptions about mental disorders and was also rather skeptical about the effectiveness of treatment or the chance of recovery for people with severe mental disorders. Nevertheless, roughly half of the students reported being willing to provide help to someone with a mental disorder when in need. Poor mental health literacy is a major barrier to seeking help and receiving effective treatment. Young people are the ideal target of raising awareness and antistigma campaigns because they are at a higher risk for developing a psychopathology

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

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

A bioinorganic approach to face two currently unsolved health issues: food poisoning and cancer

This PhD project concerns the study of metal-containing molecules with biological properties and applications. The project has been divided in two different topics: metal complexes with anti-aflatoxigenic activity and metal-based anticancer drugs as alternative to cisplatin. The common thread between the two is the use of thiosemicarbazones, versatile molecules which can be regarded both as biologically active organic molecules by themselves and also as ligands for the synthesis of metal-based drugs. The two topics have been deeply investigated using a multidisciplinary approach which combined chemical and biological experiments. The general workflow we followed consisted in a “hit-to-lead” approach. It started with the identification of promising compounds for our targets from a preliminary screening made on a large group of starting molecules. The work continued using these candidates as lead molecules for the design of a panel of derivatives, which were finally studied in detail to identify the key requirements on which the biological effect was based on and to study the different mechanisms of action. All the results we present are supported both by experimental analysis and computational calculations and many of them were found with the support of a database we built, which was very useful to combine the results that come from different fields

Antibacterial activity of metal complexes based on cinnamaldehyde thiosemicarbazone analogues

The development of microbial antibiotic resistance has become one of the biggest threats to global health and the search for new molecules active against resistant pathogenic strains is a challenge that must be tackled. In many cases nosocomial infections are caused by bacteria characterized by multi-drug resistance patterns and by their ability to produce biofilms. These properties lead to the persistence of pathogens in the hospital environment. This paper reports the synthesis and characterization of three thiosemicarbazone derivatives based on a compound containing the cinnamaldehyde natural scaffold but possessing different logPow values. These molecules are then used as ligands to prepare complexes of the Cu(II) and Zn(II) ions. All these compounds, ligands and complexes, were screened in vitro on stains of Escherichia coli and Klebsiella pneumoniae for their antibacterial activity. Despite their molecular similarity they revealed variegated behaviors. Only two of them present interesting antimicrobial properties and have also been studied to verify their stability in solution. The compound with the lowest partition coefficient is the most promising. The minimal bactericidal concentration on K. pneumoniae and E. coli of these substances are very interesting and demonstrate that the use of metalloantibiotics is a promising device to fight antibiotic resistance

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

: We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η 6 -arene)Ru(N,N0 )L][PF6 ]2 containing arene = p-cymene, N,N0 = bipyridine, and L = pyridine metawith methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)na -phthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 µM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT

Structural modification of cuminaldehyde thiosemicarbazone increases inhibition specificity toward aflatoxin biosynthesis and sclerotia development in Aspergillus flavus

Aspergillus flavus is an opportunistic mold that represents a serious threat for human and animal health due to its ability to synthesize and release, on food and feed commodities, different toxic secondary metabolites. Among them, aflatoxin B1 is one of the most dangerous since it is provided with a strong cancerogenic and mutagenic activity. Controlling fungal contamination on the different crops that may host A. flavus is considered a priority by sanitary authorities of an increasing number of countries due also to the fact that, owing to global temperature increase, the geographic areas that are expected to be prone to experience sudden A. flavus outbreaks are widening. Among the different pre- and post-harvest strategies that may be put forward in order to prevent fungal and/ormycotoxin contamination, fungicides are still considered a prominent weapon. We have here analyzed different structural modifications of a natural-derived compound (cuminaldehyde thiosemicarbazone) for their fungistatic and anti-aflatoxigenic activity. In particular, we have focused our attention on one of the compound that presented a prominent anti-aflatoxin specificity, and performed a set of physiological and molecular analyses, taking also advantage of yeast (Saccharomyces cerevisiae) cell as an experimental model

Light triggers the antiproliferative activity of naphthalimide-conjugated (η

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η -arene)Ru(N,N')L][PF ] containing arene = p-cymene, N,N' = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λ = 418 nm) compared with C1 and C2 (λ = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT)

Sabotage at the Powerhouse? Unraveling the Molecular Target of 2-Isopropylbenzaldehyde Thiosemicarbazone, a Specific Inhibitor of Aflatoxin Biosynthesis and Sclerotia Development in Aspergillus flavus, Using Yeast as a Model System

Amongst the various approaches to contain aflatoxin contamination of feed and food commodities, the use of inhibitors of fungal growth and/or toxin biosynthesis is showing great promise for the implementation or the replacement of conventional pesticide-based strategies. Several inhibition mechanisms were found taking place at different levels in the biology of the aflatoxin-producing fungal species such as Aspergillus flavus: compounds that influence aflatoxin production may block the biosynthetic pathway through the direct control of genes belonging to the aflatoxin gene cluster, or interfere with one or more of the several steps involved in the aflatoxin metabolism upstream. Recent findings pointed to mitochondrial functionality as one of the potential targets of some aflatoxin inhibitors. Additionally, we have recently reported that the effect of a compound belonging to the class of thiosemicarbazones might be related to the energy generation/carbon flow and redox homeostasis control by the fungal cell. Here, we report our investigation about a putative molecular target of the 3-isopropylbenzaldehyde thiosemicarbazone (mHtcum), using the yeast Saccharomyces cerevisiae as model system, to demonstrate how the compound can actually interfere with the mitochondrial respiratory chain