Synthesis of New DltA Inhibitors and Their Application as Adjuvant Antibiotics to Re-Sensitize Methicillin-Resistant <i>Staphylococcus aureus</i>.

ABSTRACT: The synthesis of a new acyclic and cyclic series of D-Ala-AMP analogues was reported. Chemical modifications were introduced on the carbohydrate, the sulfamate linker, and/or the amino-acid N-terminal moiety in order to increase in vivo stability and cell permeability. These new compounds were evaluated in vitro as DltA inhibitors and also in vivo as adjuvant antibiotics to re-sensitize methicillin-resistant Staphylococcus aureus. Indeed, we showed that seven nucleosides containing either a fluorine atom, an azido group, a difluorophosphonylated allylic ether moiety onto the 2'-position, or a sulfamate and a triazole as the sulfamate linker had moderate to excellent IC₅₀ values. Among all these new DltA inhibitors, two molecules functionalized

SUBMITTER: Leparfait D 

PROVIDER: S-EPMC12196251 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature