Inhibition of <i>Clostridioides difficile</i>-Specific DNA Adenine Methyltransferase CamA by Analogs of <i>S</i>‑Adenosyl‑l‑methionine.

ABSTRACT: Epigenetically targeted therapies, especially those inhibiting S-adenosyl-l-methionine (SAM)-dependent methylations of DNA, mRNA, and histones, have advanced rapidly in cancer treatment. However, these therapies remain underexplored for antibiotic development, despite the growing threat of antimicrobial resistance. Here, we screened a focused library of SAM analogs against the DNA adenine methyltransferase CamA specific to the enteric pathogen Clostridioides difficile. At the same time, we examined six other adenine methyltransferases, including two bacterial DNA methyltransferases and four human RNA methyltransferases having distinct RNA substrates. Compound 113 selectively inhibited CamA (IC₅₀ = 0.15 μM). In addition, compound 67 inhibited Caulob

SUBMITTER: Zhou J 

PROVIDER: S-EPMC12676344 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature