Search

Sepsis is a life-threatening disease that affects millions of people worldwide. Microbial infections that lead to sepsis syndrome are associated with an increased production of inflammatory molecules. Aldose reductase has recently emerged as a molecular target that is involved in various inflammatory diseases, including sepsis. Herein, a series of previously synthesized benzothiazole-based thiazolidinones that exhibited strong antibacterial and antifungal activities has been evaluated for inhibition efficacy against aldose reductase and selectivity toward aldehyde reductase under in vitro conditions. The most promising inhibitor 5 was characterized with IC50 value of 3.99 μM and a moderate selectivity. Molecular docking simulations revealed the binding mode of compounds at the active site of human aldose reductase. Moreover, owning to the absence of an acidic pharmacophore, good membrane permeation of the novel aldose reductase inhibitors was predicted. Excellent “drug-likeness” was assessed for most of the compounds by applying the criteria of Lipinski’s “rule of five”.

Therapeutic interventions with aldose reductase inhibitors appear to be a promising approach to major pathological conditions (i.e. neuropathy/angiopathy related to chronic hyperglycemia, chronic inflammation and cancer). Until now, the most potent aldose reductase inhibitors have been carboxylic acid derivatives, which poorly permeate biological membranes. In this work, continuing our previous works, we promote the bioisosteric replacement of the carboxylic acid moiety to make equally potent yet more druggable inhibitors. © 2020 Elsevier Ltd

Understanding the migration processes in the Mediterranean context requires taking into account the massive population movements after the collapse of empires in the early twentieth century, the post-WWII migration from Southern to Northern Europe, the migrant flows created by the political upheavals in Eastern Europe in 1989 and the recent refugee influx from Asian and North African countries. This chapter provides empirical insight into the prevailing situation of temporary migration between Greece and Asian countries. We present an analysis of the politico-legal, socio-economic and sociocultural aspects of this migration process. We argue that in a country where the labour market lacks permanent employment opportunities and where there are rapid political changes, the integration of immigrants into a state of temporariness reaches extremes. .