The design of novel classes of macrolides for neutrophil-dominated inflammatory diseases

Neutrophil-dominated inflammatory diseases, like chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, bronchiolitis obliteras syndrome and non-eosinophilic asthma, present a significant medical problem lacking adequate therapy. Macrolide antibiotics have been reported to be effective in the treatment of the aforementioned diseases, for reasons unrelated to their antibacterial action. This has resulted in research activities aimed at gaining a better understanding of the immunomodulatory actions of macrolides and the synthesis of various novel anti-inflammatory macrolides without antimicrobial activity. Despite the difficult chemistry and lack of an extensive knowledge for their mechanism of action, several interesting molecules from this class, including potential clinical candidates, are on the horizon.