Search

Phosphodiesterase 4 (PDE4) enzymes catalyze cyclic adenosine monophosphate (cAMP) hydrolysis and are involved in a variety of physiological processes, including brain function, monocyte and macrophage activation, and neutrophil infiltration. Among different PDE4 isoforms, Phosphodiesterases 4D (PDE4Ds) play a fundamental role in cognitive, learning and memory consolidation processes and cancer development. Selective PDE4D inhibitors (PDE4Dis) could represent an innovative and valid therapeutic strategy for the treatment of various neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and Lou Gehrig's diseases, but also for stroke, traumatic brain and spinal cord injury, mild cognitive impairment, and all demyelinating diseases such as multiple sclerosis. In addition, small molecules able to block PDE4D isoforms have been recently studied for the treatment of specific cancer types, particularly hepatocellular carcinoma and breast cancer. This review overviews the PDE4DIsso far identified and provides useful information, from a medicinal chemistry point of view, for the development of a novel series of compounds with improved pharmacological properties. [ABSTRACT FROM AUTHOR]

The systems for hospitality and social inclusion of migrants in Italy offer a privileged point of view for debating about language education policies. The challenge of literacy education and second language learning for young people and adults who are illiterate or scarcely literate and uneducated or scarcely educated requires thinking accurately about the impact one's actions have in the pre-A1 level classes. The specific needs of asylum seekers and refugees may lead teachers to adopt means and attitudes of community-building, which could be useful even in a broader educational environment, and may be a chance to re-evaluate the political potential of literacy. We propose a path for literacy education where the aims are driven by the students' needs of self-determination and involvement in our society: it is necessary to acquire oral competence in Italian as a second language, to develop the semiotic system of writing, to acquire phonological awareness, to master the use of pencil and paper, to understand what is written all around you. The proposal, rooted in acquisitional linguistics research, is intended to create a safe community environment, fruitful for interaction and learning. The development of this model is possible when the teacher and the students work and play together, and the class becomes a societal structure in which everybody takes part. Literacy classes can therefore become a training ground for democratic participation in society. [ABSTRACT FROM AUTHOR]

In previous studies, we synthesized different imidazo-pyrazoles 1 and 2 with interesting anticancer, anti-angiogenic and anti-inflammatory activities. To further extend the structure-activity relationships of imidazo-pyrazole scaffold and to identify novel antiproliferative/anti-inflammatory agents potentially active with multi-target mechanisms, a library of compounds 3-5 has been designed and synthesized. The chemical modifications characterizing the novel derivatives include: i) decoration of the catechol ring with groups with different electronic, steric and lipophilic properties (compounds 3); ii) insertion of a methyl group on C-6 of imidazo-pyrazole scaffold (compounds 4); iii) shift of the acylhydrazonic substituent from position 7 to 6 of the imidazo-pyrazole substructure (compounds 5). All synthesized compounds were tested against a panel of cancer and normal cell lines. Derivatives 3 a, 3 e, 4 c, 5 g and 5 h showed IC 50 values in the low micromolar range against selected tumor cell lines and proved to have antioxidant properties, being able to inhibit ROS production in human platelet. In silico calculation predicted favourable drug-like and pharmacokinetic properties for the most promising compounds. Furthermore, molecular docking and molecular dynamic simulations suggested the ability of most active derivative 3 e to interact with colchicine binding site in the polymeric tubulin α/tubulin β/stathmin4 complex., (© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)