Semisynthesis and Biological Evaluation of Platencin Thioether Derivatives: Dual FabF and FabH Inhibitors against MRSA.

ABSTRACT: The discovery and clinical use of multitarget monotherapeutic antibiotics is regarded as a promising approach to reduce the development of antibiotic resistance. Platencin (PTN), a potent natural antibiotic initially isolated from a soil actinomycete, targets both FabH and FabF, the initiation and elongation condensing enzymes for bacterial fatty acid biosynthesis. However, its further clinical development has been hampered by poor pharmacokinetics. Herein we report the semisynthesis and biological evaluation of platencin derivatives 1-15 with potent antibacterial activity against methicillin-resistant Staphylococcus aureus in vitro. Some of these PTN analogues showed similar yet distinct interactions with FabH and FabF, as shown by molecular docking, differential scan

SUBMITTER: Li Y 

PROVIDER: S-EPMC7957939 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature