Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Anti-Bacterial Agents chemical synthesis chemistry pharmacology MeSH
- Apoptosis drug effects MeSH
- Cell Membrane metabolism MeSH
- Cell Line MeSH
- Phospholipids chemistry MeSH
- Gram-Negative Bacteria drug effects MeSH
- Gram-Positive Bacteria drug effects MeSH
- Rabbits MeSH
- Humans MeSH
- Lipid Bilayers chemistry MeSH
- Microbial Sensitivity Tests MeSH
- Drug Resistance, Multiple, Bacterial MeSH
- Mice, Inbred ICR MeSH
- Cell Line, Tumor MeSH
- Pyrazoles chemical synthesis chemistry pharmacology MeSH
- Drug Design MeSH
- Stereoisomerism MeSH
- Skin Irritancy Tests MeSH
- Uridine Monophosphate analogs & derivatives chemical synthesis chemistry pharmacology MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- Phospholipids MeSH
- Lipid Bilayers MeSH
- Pyrazoles MeSH
- Uridine Monophosphate MeSH
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.
References provided by Crossref.org
Lipophosphonoxins-A Novel Group of Broad Spectrum Antibacterial Compounds
LEGO-Lipophosphonoxins: A Novel Approach in Designing Membrane Targeting Antimicrobials
Evaluation of Second-Generation Lipophosphonoxins as Antimicrobial Additives in Bone Cement
Colicin U from Shigella boydii Forms Voltage-Dependent Pores
