Synthesized Bis-Triphenyl Phosphonium-Based Nano Vesicles Have Potent and Selective Antibacterial Effects on Several...

Area of Science:

• Medicinal Chemistry
• Antimicrobial Agents
• Nanotechnology

Background:

• Rising multidrug-resistant (MDR) pathogens necessitate novel antimicrobial strategies.
• Quaternary phosphonium salts (QPSs) show antimicrobial potential but are less studied than quaternary ammonium salts (QASs).
• Previous work demonstrated bacteriostatic and cytotoxic effects of a triphenyl phosphonium salt against MDR Gram-positive bacteria.

Purpose of the Study:

• To synthesize and evaluate a novel, water-soluble, sterically hindered quaternary phosphonium salt (BPPB) for broad-spectrum antibacterial activity.
• To investigate the self-assembly properties and physicochemical characteristics of BPPB.
• To assess the antibacterial efficacy and cytotoxicity of BPPB against clinically relevant MDR pathogens.

Main Methods:

• Synthesis of BPPB, a bola-amphiphilic molecule with two triphenyl phosphonium groups.
• Characterization using spectroscopic techniques (ATR-FTIR, NMR, UV), mass spectrometry (FIA-MS), elemental analysis, and potentiometric titrations.
• Evaluation of self-assembly (vesicle formation) using DLS and optical microscopy, and zeta potential measurement.
• Determination of Minimum Inhibitory Concentrations (MICs) against 50 clinical isolates of Gram-positive and Gram-negative bacteria.
• Assessment of cytotoxicity against HepG2 (human hepatic) and Cos-7 (monkey kidney) cell lines.

Main Results:

• BPPB self-assembles into 45 nm spherical vesicles in dilute solutions, exhibiting a positive zeta potential (+18 mV).
• Excellent broad-spectrum antibacterial activity was observed against all tested clinical isolates, including ESKAPE pathogens.
• MIC values ranged from 0.250 µg/mL to 32 µg/mL, with the highest values against MDR Gram-negative bacteria resistant to last-resort antibiotics (colistin, carbapenems, cefiderocol).
• BPPB demonstrated favorable selectivity indices (>10) against Gram-positive bacteria and key Gram-negative pathogens like *E. coli*.

Conclusions:

• The synthesized bola-amphiphilic phosphonium salt, BPPB, exhibits potent broad-spectrum antibacterial activity.
• BPPB shows promising efficacy against highly resistant Gram-negative bacteria, addressing a critical unmet medical need.
• The favorable safety profile and potent activity make BPPB a promising candidate for further clinical development as a novel antibacterial agent.