Tarek Aboul-Fadl
Assiut University, Egypt
Title: Novel Synthetic Inhibitors of Eosinophils with Potential Anti-asthmatic Activity
Biography
Biography: Tarek Aboul-Fadl
Abstract
Asthma is a major public health issue with high and increasing prevalence rates and a concomitant increase in morbidity and mortality. Asthma is estimated to affect 300 million people, with an expected increase to 400 million worldwide by 2025. Many factors may have contributed to the rise of the problem of bronchial asthma. Increasing air pollution, fast modernization, and widespread construction work are some of the reasons for asthma to thrive. The situation is complicated by poor access to medical services and high price of effective drugs. Asthma is a chronic inflammatory condition, triggered by environmental factors in genetically predisposed individuals, and is characterized by mast cell, T lymphocyte, and eosinophil infiltrates in the bronchial mucosa. Eosinophils are recruited to sites of specific inflammatory reactions, especially during allergic diseases and are correlated with asthma severity. In spite of their numerous adverse effects inhaled glucocortocoids have been established as the standard treatment for asthma. Therefore, an urgent need exists for alternative treatments to overcome these undesirable side effects of steroid therapy and to provide another effective agent for the treatment of asthma. Lidocaine inhibits interleukin-5 (IL-5)-mediated survival and activation of human eosinophils, and it is able to replace inhaled glucocorticoids for the treatment of asthma; however, lidocaine has many undesired side effects mainly due to its sodium channel activity including anesthesia. Accordingly, the current work aims to modify lidocaine structure to obtain analogs with minimum sodium channel IL-5 inhibitory activity. The hypothesis supported by ligand-based pharmacophore modeling generated using different molecular modeling programs.