Novel Indane-Containing NBTIs with Potent Anti-Gram-Negative Activity and Minimal hERG Inhibition.

ABSTRACT: Novel bacterial topoisomerase inhibitors (NBTIs) make up a promising new class of antibiotics with the potential to combat the growing threat of antimicrobial resistance. Two key challenges in the development of NBTIs have been to obtain broad spectrum activity against multidrug-resistant Gram-negative bacteria and to diminish inhibition of the hERG cardiac ion channel. Here we report the optimization of a series of NBTIs bearing a novel indane DNA intercalating moiety. The addition of a basic, polar side chain connected to the indane by an ether or an N-linked secondary amide linkage together with a lipophilicity-lowering modification of the enzyme binding moiety led to compounds such as 2a and 2g which showed excellent broad spectrum potency and minimal hERG inhibiti

SUBMITTER: Cumming JG 

PROVIDER: S-EPMC10726470 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature