Development of triaryl antimicrobials by scaffold hopping from an aminopropanol hit targeting bacterial RNA polymerase-NusG interactions.

ABSTRACT: Bacterial RNA polymerase (RNAP) requires the NusG factor to facilitate transcription, with the RNAP clamp-helix domain (CH) serving as the primary binding site for NusG and representing a promising target for antimicrobial intervention. In previous work, we unprecedentedly developed a pharmacophore model based on key clamp-helix residues (R270, R278, R281) at RNAP CH essential for NusG binding, which led to the identification of a hit compound exhibiting modest antimicrobial activity against Streptococcus pneumoniae. In this study, we designed a new class of triaryl inhibitors via scaffold hopping, substituting the linear structure of the hit compound with a benzene ring. Antimicrobial testing showed that several newly synthesised lead compounds achieved the minimum inhibitory conce

SUBMITTER: Liu T 

PROVIDER: S-EPMC12364105 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature