Design, Synthesis, and Evaluation of Novel Inhibitors of Aminoglycoside-Resistance 16S Ribosomal RNA Methyltransferases.

ABSTRACT: One of the major mechanisms of resistance to ribosome-targeting antibiotics is the modification of ribosomal RNA (rRNA). Specific methyltransferase enzymes, for example, confer high-level resistance to aminoglycosides by selectively methylating the 16S rRNA in the ribosomal decoding center. These enzymes have been detected globally and pose a threat to the continued use of aminoglycosides. Compound 1, a dehydroamino amide inhibitor of the m¹A1408 methyltransferase NpmA, was previously disclosed and identified using high-throughput virtual screening. Here, the synthesis and biological evaluation of rationally designed analogs of 1 has been reported. Guided by molecular docking, additional putative inhibitors of NpmA, as well as the functionally related m⁷G1405 methyltr

SUBMITTER: Deprez BE 

PROVIDER: S-EPMC12698113 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature