1 research outputs found
Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents
The
increase in the number of bacterial strains resistant to known
antibiotics is alarming. In this study we report the synthesis of
novel compounds termed Lipophosphonoxins II (LPPO II). We show that
LPPO II display excellent activities against Gram-positive and -negative
bacteria, including pathogens and multiresistant strains. We describe
their mechanism of action–plasmatic membrane pore-forming activity
selective for bacteria. Importantly, LPPO II neither damage nor cross
the eukaryotic plasmatic membrane at their bactericidal concentrations.
Further, we demonstrate LPPO II have low propensity for resistance
development, likely due to their rapid membrane-targeting mode of
action. Finally, we reveal that LPPO II are not toxic to either eukaryotic
cells or model animals when administered orally or topically. Collectively,
these results suggest that LPPO II are highly promising compounds
for development into pharmaceuticals