Therapeutics for drug resistant-bacteria: Arylpropionyl-phloroglucinols

In preliminary work, we have identified a novel class of broad-spectrum antibacterial agents: arylpropionyl phloroglucinols (APPs). APPs potently inhibit bacterial RNA polymerase (RNAP)~but not mammalian RNAP~in vitro, potently inhibit bacterial growth in culture, and potently clear infection in a mouse model of methicillin-resistant Staphylococcus aureus infection. APPs exhibit antibacterial activity against both Gram-positive and Gram-negative bacterial pathogens, including drug-sensitive, beta-lactam-resistant, macrolide-resistant, tetracycline-resistant, rifampin-resistant, vancomycin-resistant, and multi-drug-resistant Staphylococcus aureus, Enterococcus faecalis, NIAID category A pathogen Bacillus anthracis, NIAID category A pathogen Francisella tularensis, and NIAID category B pathogen Brucella melitensis. APPs exhibit no cross-resistance with rifampin, the RNAP inhibitor in current use in broad-spectrum antibacterial therapy, and exhibit a spontaneous resistance rate