Macrolide Structure, Bioactivity and Interactions: a Review

Since the discovery of macrolide antibiotics, extensive research has been focused on the development of new bioactive compounds in response to an emerging number of multidrug-resistant pathogens. In the last several decades, macrolide antibiotics have made a significant contribution to human healthcare. Nevertheless, interest in the development of broad-spectrum macrolides remains due to increasing bacterial resistance. This review summarizes recent advances in macrolide synthesis and discusses alternative strategies for structural modification of macrolides, highlighting how these modifications affect their bioactivity through structure-activity relationship (SAR) and interaction studies. It provides an insight into the macrolide binding mechanisms to their biomolecular targets that play key roles in the overall biological profile of a drug. Recently reported structures of macrolide complexes with biomolecules have also been summarized, providing a platform for the design of new antibiotics active against resistant bacteria.