Small Antimicrobial Agents Based on Acylated Reduced Amide Scaffold

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.