ORCID Profile
0000-0003-0664-714X
Current Organisation
University of Vienna
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 15-10-2018
DOI: 10.1038/S41419-018-1102-Z
Abstract: Due to their high biological activity, thiosemicarbazones have been developed for treatment of erse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest based on their enhanced cytotoxic activity. Increasing evidence suggests that the double-dimethylated Triapine derivative Me 2 NNMe 2 differs from Triapine not only in its efficacy but also in its mode of action. Here we show that Me 2 NNMe 2 - (but not Triapine)-treated cancer cells exhibit all hallmarks of paraptotic cell death including, besides the appearance of endoplasmic reticulum (ER)-derived vesicles, also mitochondrial swelling and caspase-independent cell death via the MAPK signaling pathway. Subsequently, we uncover that the copper complex of Me 2 NNMe 2 (a supposed intracellular metabolite) inhibits the ER-resident protein disulfide isomerase, resulting in a specific form of ER stress based on disruption of the Ca 2+ and ER thiol redox homeostasis. Our findings indicate that compounds like Me 2 NNMe 2 are of interest especially for the treatment of apoptosis-resistant cancer and provide new insights into mechanisms underlying drug-induced paraptosis.
Publisher: Mary Ann Liebert Inc
Date: 20-08-2020
Publisher: Springer Science and Business Media LLC
Date: 08-12-2007
DOI: 10.1007/S10071-007-0125-0
Abstract: We compared the mobbing response to model snakes of two groups of captive-born common marmosets (Callithrix jacchus) differing in genetic relatedness, age and past experience. Mobbing vocalisations (tsik calls), other mobbing behaviour and attention to the stimulus were recorded for 2 min. intervals pre-exposure, during exposure to various stimuli and post-exposure. Marmosets in one group were vocally reactive to all stimuli, although more so to one particular stimulus resembling rearing snakes and modified images of it, whereas the marmosets in a younger and genetically unrelated group attended to the stimuli but made very few mobbing calls. The parent stock of the first group had suffered stress in early life and had developed a phobic response to a specific stimulus, which they had transmitted to their offspring. A third group, matching the older group in age range but genetically unrelated, was also found to be unresponsive to the stimulus that elicited the strongest response in the first group. Cortisol levels in s les of hair were assayed and a significant negative correlation was found between the number of tsik calls made during presentation of the stimuli and the cortisol level, showing that mobbing behaviour/behavioural reactivity is associated with low levels of physiological stress.
Publisher: American Chemical Society (ACS)
Date: 10-08-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0DT03465G
Abstract: Effect of exchange of S to O or Se in Triapine and methylation of the hydrazone NH on the p K a , lipophilicity, solution stability and redox properties of Cu( ii ), Fe( ii ) and Fe( iii ) complexes and their anticancer activity.
Publisher: SAGE Publications
Date: 13-08-2015
Abstract: While smiling enhances women’s facial attractiveness, the findings are inconclusive for men. The present study investigated the effect of smiling on male facial attractiveness for short- and long-term prospective partners using East Asian and European s les. In Experiment 1 ( N = 218), where female participants rated male facial attractiveness, the facilitative effect of smiling was present when judging long-term partners but absent for short-term partners. This pattern was observed for East Asians as well as for Europeans. Experiment 2 ( N = 71) demonstrated that smiling male faces engendered an impression suitable for long-term partnership (e.g., high ratings of trustworthiness) while neutral faces produced an impression suitable for short-term partnership (e.g., high ratings of masculinity). We discuss these results in terms of opposing evolutionary strategies in mate choice: heritable benefit versus paternal investment.
Publisher: Mary Ann Liebert Inc
Date: 10-03-2019
Abstract: During the past decades, thiosemicarbazones were clinically developed for a variety of diseases, including tuberculosis, viral infections, malaria, and cancer. With regard to malignant diseases, the class of α-N-heterocyclic thiosemicarbazones, and here especially 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine), was intensively developed in multiple clinical phase I/II trials. Recent Advances: Very recently, two new derivatives, namely COTI-2 and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) have entered phase I evaluation. Based on the strong metal-chelating/metal-interacting properties of thiosemicarbazones, interference with the cellular iron (and copper) homeostasis is assumed to play an important role in their biological activity. In this review, we summarize and analyze the data on the interaction of (α-N-heterocyclic) thiosemicarbazones with iron, with the special aim of bridging the current knowledge on their mode of action from chemistry to (cell) biology. In addition, we highlight the difference to classical iron(III) chelators such as desferrioxamine (DFO), which are used for the treatment of iron overload. We want to emphasize that thiosemicarbazones are not solely removing iron from the cells/organism. In contrast, they should be considered as iron-interacting drugs influencing erse biological pathways in a complex and multi-faceted mode of action. Consequently, in addition to the discussion of physicochemical properties (e.g., complex stability, redox activity), this review contains an overview on the ersity of cellular thiosemicarbazone targets and drug resistance mechanisms.
Location: Austria
No related grants have been discovered for Luca Tommasi.