Repurposing the antihistamine terfenadine for antimicrobial activity against Staphylococcus aureus.

ABSTRACT: Staphylococcus aureus is a rapidly growing health threat in the U.S., with resistance to several commonly prescribed treatments. A high-throughput screen identified the antihistamine terfenadine to possess, previously unreported, antimicrobial activity against S. aureus and other Gram-positive bacteria. In an effort to repurpose this drug, structure-activity relationship studies yielded 84 terfenadine-based analogues with several modifications providing increased activity versus S. aureus and other bacterial pathogens, including Mycobacterium tuberculosis. Mechanism of action studies revealed these compounds to exert their antibacterial effects, at least in part, through inhibition of the bacterial type II topoisomerases. This scaffold suffers from hERG liabilities which were not remedied

SUBMITTER: Perlmutter JI 

PROVIDER: S-EPMC4207543 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature