Creation of a macrolide antibiotic against non-tuberculous <i>Mycobacterium</i> using late-stage boron-mediated aglycon delivery.

ABSTRACT: Non-tuberculous mycobacteria (NTM) is gaining clinical recognition as a recently emerging pulmonary pathogen. Mycobacterium avium complex (MAC), the most common NTM, is the cause of pulmonary MAC disease. Currently, the macrolide azithromycin (AZM) is the standard first-line antibiotic for treatment of the disease. However, the rise of drug-resistant MAC necessitates the development of alternative therapeutics. Here, we present a late-stage boron-mediated aglycon delivery strategy for selective modification of AZM, generating a library of potential anti-MAC drugs designated KU01 to KU13. Screening of KU01 to KU13 revealed that KU13 exhibited enhanced antimicrobial activity against wild-type and macrolide-resistant MAC compared to AZM. Cryo-electron

SUBMITTER: Isozaki Y 

PROVIDER: S-EPMC11881915 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature