The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

Rhodanines, as one of the 4-thiazolidinones subtypes, are recognized as privileged heterocycles in medicinal chemistry. The main achievements include the development of drug-like molecules with numerous biological activities as well as approved drugs. Among rhodanines, 5-ene-rhodanines are of special interest, and are often claimed as pan assay interference compounds due to Michael acceptor functionality. Areas covered: Herein, the synthetic protocols for rhodanines and their transformation are reviewed. Biological activity is briefly discussed as well as biotargets, mode of actions and optimization directions. Furthermore, the utilization of 5-ene-rhodanines in Michael additions are discussed while both pro and contra arguments have been outlined within medicinal chemistry application. Expert opinion: Rhodanines remain privileged heterocycles in drug discovery. They are accessible building blocks for optimization and transformation into related heterocycles, simplified analogues and fused heterocycles with a thiazolidine framework. Michael acceptor functionality, as well as the thesis about low selectivity towards biotargets of rhodanines, must be confirmed experimentally and it cannot be based on just the presence of conjugated α,β-unsaturated carbonyl. Moreover, the positive aspects of Michael acceptors must be considered as well as their multitarget properties. New criteria for target affinity must be found. In conclusion, rhodanines are generally not problematic per se.

Here, we describe the synthesis and anticonvulsant activity of thiazole-bearing hybrids based on 2-imino-4-thiazolidinone and 2,4-dioxothiazolidine-5-carboxylic acid cores. The structure of target compounds was based on the following: (i) A combination of two thiazole cores; (ii) similarity to ralitolin’s structure; (iii) the compliance with structural requirements for the new anticonvulsants. Target compounds were synthesized via known approaches based on Knoenavegel reaction, alkylation reaction, and one-pot three-component reaction. Anticonvulsant properties of compounds were evaluated in two different models—pentylenetetrazole-induced seizures and maximal electroshock seizure tests. Among the tested compounds 5Z-(3-nitrobenzylidene)-2-(thiazol-2-ylimino)-thiazolidin-4-one Ib, 2-[2,4-dioxo-5-(thiazol-2- ylcarbamoylmethyl)-thiazolidin-3-yl]-N-(2-trifluoromethylphenyl)acetamide IId and (2,4-dioxo-5- (thiazol-2-ylcarbamoylmethylene)-thiazolidin-3-yl)acetic acid ethyl ester IIj showed excellent anticonvulsant activity in both models. The directions of compounds modification based on SAR aspects were discussed. The results of the study provide a basis for further study of the anticonvulsant properties of selected thiazole-thiazolidinones.