Synthetic Antibacterial Quaternary Phosphorus Salts Promote Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing

Abstract

Background: Drug-resistant microbes pose a global health concern, requiring the urgent development of effective antibacterial agents and strategies in clinical practice. Therefore, there is an urgent need to explore novel antibacterial materials to effectively eliminate bacteria. The synthesis of quaternary phosphonium salt in haloargentate systems, wherein the phosphorus atom is represented in a cationic form, is a possible strategy for the development of antibacterial materials. Methods: Using (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 4, 6) as a template, we designed three kinds of quaternary phosphorus salts as effective antibacterial agents against drug-resistant bacteria. Results:The synthesized quaternary phosphorus salt of (1,4-DBTPP)Br 2 effectively prevented the formation of the bacterial biofilms, and degraded bacterial membranes and cell walls by promoting the production of reactive oxygen species, which exhibited effective therapeutic effects in a rat model of a superficial wound infected with methicillin-resistant Staphylococcus aureus. Conclusion:The quaternary phosphorus salt (1,4-DBTPP)Br 2 demonstrated hemocompatibility and low toxicity, revealing its potential in the treatment of clinical infections.

Anti Gram-Positive Bacteria Activity of Synthetic Quaternary Ammonium Lipid and Its Precursor Phosphonium Salt

“…On the other hand, the MICs of compounds developed by these authors were remarkably higher (64–128 µg/mL) than those determined by us for 1 and 6 against MRSA, and according to our criteria, at the threshold of inactivity. In fact, the MICs we reported for 1 (4 μg/mL) were in general significantly lower, and even considering the best-performing compound developed by Shi et al (4C) [ 45 ], 1 was 4 times more potent, thus suggesting that the antibacterial activity of QPS could not be associated with the number of cationic parts. Additionally, against MRSA, compound 1 displayed similar to higher antibacterial activity than five out of six multi-QACs developed by Vereshchagin et al and displayed equal antibacterial activity to commercially available chlorhexidine digluconate [ 19 ].…”

Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms

“…Furthermore, this year, Shi et al reported on the synthesis, characterization, and microbiological evaluation of alkyl-bis-(triphenyl) phosphonium bromides, namely (1,2-DBTPP)Br 2 , (1,4-DBTPP)Br 2 , and (1,6-DBTPP)Br 2 . The biological results revealed that the butyl derivative (1,4-DBTPP)Br 2 exhibited low toxicity and low hemolytic activity on eukaryotic cells and the capability to inhibit bacterial growth and BF formation and to promote the recovery process of infected wounds in vivo [ 173 ].…”

“…Scheme 8. Synthesis of alkyl-bis-(triphenyl) phosphonium bromides (1,2-DBTPP)Br 2 , (1,4-DBTPP)Br 2 , and (1,6-DBTPP)Br 2[173]. n = 2, 4, 6.…”

6-Aza-2-Thiothymine-Capped Gold Nanoclusters as Robust Antimicrobial Nanoagents for Eradicating Multidrug-Resistant Escherichia coli Infection

“…Yang et al reported a kind of AMP with cationic and amphiphilic structures, which can disintegrate Gram-negative bacteria via inserting into their cell surfaces . Compared with conventional antibiotics, one of the strengths of AMPs is their low propensity for resistance development; however, AMPs show high cost and hemolysis in vivo, and the poor antibacterial activity and salt instability also limit their clinical implementation . In fact, a relatively new field of nanotechnology has opened the new possibilities of designing effective formulations for fighting antibiotic resistance …”

“…5 Compared with conventional antibiotics, one of the strengths of AMPs is their low propensity for resistance development; however, AMPs show high cost and hemolysis in vivo, and the poor antibacterial activity and salt instability also limit their clinical implementation. 6 In fact, a relatively new field of nanotechnology has opened the new possibilities of designing effective formulations for fighting antibiotic resistance. 7 Metal-based antibacterial therapeutics, such as silver nanoparticles, 8 ZnO nanoparticles, 9 and iron oxide nanoparticles, 10,11 have attracted growing interest due to their efficiency of antimicrobial properties, no resistance development, and convenient for transporting.…”