New histamine H4 ligands as potential anti-allergic and anti-inflammatory drugs

The aim of the project is to search for compounds characterized by high activity and specificity for the histamine H4 receptor by means of molecular modeling methods, synthesis of selected compounds, receptor studies, characterization of their cytotoxicity and genotoxicity, and analysis of potential anti-allergic and anti-inflammatory properties in vitro. H4 receptors are located primarily on cells of hematopoietic origin, e.g. eosinophils, mast cells, basophils, neutrophils, dendritic cells, monocytes, T lymphocytes, and participate in many inflammatory processes; therefore, the H4 receptor is considered a molecular target for drugs used in the treatment of diseases immune systems such as allergies, asthma and autoimmune diseases. As both the histamine HI and H4 receptor antagonists have anti-inflammatory and antiallergic properties, a synergistic effect was also found between the HI and H4 receptors; therefore, an additional project goal will be to search for double ligands for H1/H4 receptors. These ligands can be both different chemical structures linked by a linker as well as a uniform chemical structure designed using the knowledge of the binding sites of H1 and H4 receptors. The aim of the project is also to build a model of the H1/H4 heterodimer and to understand the mechanisms of action of selected compounds on the H4 receptor and the H1/H4 heterodimer.