Figure 6.

Synergistic mechanism of action proposed for P-113 derivatives and vancomycin. For vancomycin, the efficacy was limited due to the permeability barrier of the outer membrane of Gram-negative bacteria (left panel). However, P-113 derivatives (e.g., Bip-P-113, Dip-P-113, and Nal-P-113) could disturb the outer membrane of Gram-negative bacteria and enhance the entry of vancomycin into these bacteria (right panel). Moreover, P-113 derivatives could bind and neutralize LPS through extra hydrophobic interactions with the lipid A motif of LPS (right panel).