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  • Title: Small Antimicrobial Agents Based on Acylated Reduced Amide Scaffold.
    Author: Teng P, Huo D, Nimmagadda A, Wu J, She F, Su M, Lin X, Yan J, Cao A, Xi C, Hu Y, Cai J.
    Journal: J Med Chem; 2016 Sep 08; 59(17):7877-87. PubMed ID: 27526720.
    Abstract:
    Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resistant Gram-positive and Gram-negative bacterial strains. Meanwhile, they also effectively inhibit the biofilm formation. Mechanistic studies suggest that these compounds kill bacteria by compromising bacterial membranes, a mechanism analogous to that of host-defense peptides (HDPs). The mechanism is further supported by the fact that the lead compounds do not induce resistance in MRSA bacteria even after 14 passages. Lastly, we also demonstrate that these molecules have therapeutic potential by preventing inflammation caused by MRSA induced pneumonia in a rat model. This class of compounds could lead to an appealing class of antibiotic agents combating drug-resistant bacterial strains.
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