1,721,105 research outputs found
Environmental Disasters and Electoral Cycle: An Empirical Analysis on Floods and Landslides in Italy
No full textThe aim of this paper is to analyse potential drivers of land use policy, in the form of building permits issued in Italian provinces. We first derive testable implications on the basis of a standard political agency framework, augmented to account for the impact of past environmental disasters (floods, landslides and earthquakes) and for the relevance of “building permits intensive” sectors in determining voters’ support to an incumbent politician. We then perform an empirical analysis that tests theoretical predictions using a unique dataset covering Italy in the period 2001–2012. Our main conclusions show that the occurrence of floods and earthquakes decreases building permits, implying that a bad history in terms of these phenomena strengthens the importance of voters affected by past disasters. No corresponding evidence seems to emerge with reference to landslides. On the other hand, the relevance of the construction sector increases the number of building permits issued. Finally, when elections approach, the number of building permits issued grows, suggesting that incumbent politicians may distort land use policies in order to favour “brown” voters in periods close to elections
Interplay Between Endocannabinoid System and Neurodegeneration: Focus on Polypharmacology
Full text linkPharmacological treatment of complex pathologies, such as neurodegenerative diseases still represents a major challenge, due to the networked pathways involved in their onset and progression that may require equally complex therapeutic approaches. Polypharmacology, based on the simultaneous modulation of multiple targets involved in the disease, may offer the potential to increase effectiveness and reduce the drawbacks related to the use of drug combinations. Clearly, this approach requires both the knowledge of the systems responsible for disease development and the discovery of new attractive targets to be exploited to design a multitarget drug. Over the last years, an ever increasing interest has focused on the endocannabinoid system, implicated in the modulation of several physiological functions, among which neuroinflammation, a crucial process for most neurodegenerative diseases. In this respect, the cannabinoid receptor subtype 2 represents a promising therapeutic target, being overexpressed in microglia cells and thus involved in neuroinflammation. The indirect modulation of this system through the inhibition of the main enzymes responsible for endocannabinoids metabolism, namely fatty acid amide hydrolase and monoacylglycerol lipase, may also significantly affect neurodegenerative processes. The aim of this review is to give an overview of the opportunities posed by the endocannabinoid system for neurodegenerative diseases management, mainly focusing on the potential for a multitarget strategy
Naturally Inspired Coumarin Derivatives in Alzheimer’s Disease Drug Discovery: Latest Advances and Current Challenges
Full text linkThe main feature of neurodegenerative diseases, including Alzheimer's disease, is the network of complex and not fully recognized neuronal pathways and targets involved in their onset and progression. The therapeutic treatment, at present mainly symptomatic, could benefit from a polypharmacological approach based on the development of a single molecular entity designed to simultaneously modulate different validated biological targets. This strategy is principally based on molecular hybridization, obtained by linking or merging different chemical moieties acting with synergistic and/or complementary mechanisms. The coumarin core, widely found in nature, endowed with a recognized broad spectrum of pharmacological activities, large synthetic accessibility and favourable pharmacokinetic properties, appears as a valuable, privileged scaffold to be properly modified in order to obtain compounds able to engage different selected targets. The scientific literature has long been interested in the multifaceted profiles of coumarin derivatives, and in this review, a survey of the most important results of the last four years, on both natural and synthetic coumarin-based compounds, regarding the development of anti-Alzheimer's compounds is reported
4-Heterotricyclic substituted 1,4-dihydropyridines with a potent selective bradycardic effect
No full textA series of 4-heterotricyclic substituted 1,4-dihydropyridines were prepared. The compounds were evaluated for inotropic, chronotropic and calcium antagonist properties. The tested compounds are fairly good as calcium antagonists, but exert potent selective bradycardic effects
Flavonoid-inspired vascular disrupting agents: Exploring flavone-8-acetic acid and derivatives in the new century
Full text linkNaturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due to the versatility of the scaffolds and the vast possibilities of appropriate decoration, they have also been regarded as fruitful sources of lead compounds and excellent chemical platforms for the development of bioactive synthetic compounds. Flavone-8-acetic acid (FAA) and 5,6-dimethylxanthone acetic acid (DMXAA) emerged for their antitumour potential due to the induction of cytokines and consequent rapid haemorrhagic necrosis of murine tumour vasculature, and different series of derivatives have been designed thereafter. Although the promising DMXAA failed in phase III clinical trials because of strict species-specificity, a boost in research came from the recent identification of the stimulator of interferon genes (STING), responsible for supporting tumoural innate immune responses, as a possible biological target. Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Un-doubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective
Fluorenone and benzophenone 1,4-dihydropyridine derivatives with cardiodepressant activity
No full textA series of fluorenone and benzophenone 1,4-dihydropyridine derivatives were prepared. The compounds were evaluated for inotropic, chronotropic and calcium antagonist properties
Negative inotropic and chronotropic activity of calcium channel ligands possessing a xanthone 1,4-dihydropyridine backbone
No full textA series of xanthone 1,4-dihydropyridine derivatives were prepared. The compounds were evaluated for inotropic, chronotropic, and calcium antagonist properties
Reconsidering Aromatase for Breast Cancer Treatment: New Roles for an Old Target
Full text linkThe current therapeutic approach for the treatment of hormone dependent breast cancer includes interference with estrogen receptors via either selective modulators or estrogens deprivation, by preventing their biosynthesis with aromatase inhibitors. Severe side effects and acquired resistance are drawbacks of both drug classes, and the efforts to overcome these issues still allow for research in this field to be animated. This review reports on recent findings that have opened new avenues for reconsidering the role of aromatase enzymes (and estrogen receptors) leading to the possibility of looking at well-known targets in a new perspective
- …
