Synthesis of triphenylphosphine pillar[5]arene with inhibitory effect on Staphylococcus aureus

Abstract:

Staphylococcus aureus is one of the common pathogens causing infections. It can attach media or implant surfaces to form biofilms, which makes it difficult to be tackled and leads to the generation of drug resistance, posing a great challenge to clinical treatment. Therefore, it is urgent to develop novel antimicrobials. Pillar[5]arenes, a new class of supramolecular macrocyclic hosts, attracting wide attention due to their highly rigid and symmetrical architectures and controllable cavity sizes, which afford the limitless possibility to create antimicrobial agents with various functional groups and biological activities. [Objective] To synthesize triphenylphosphine pillar[5]arene (TPP) and determine its antibacterial activities and drug resistance with Staphylococcus aureus ATCC 6538, Staphylococcus aureus subsp. aureus (S. subsp. aureus) ATCC 29213, and methicillin-resistant S. aureus ATCC 43300. [Methods] The minimal inhibitory concentration (MIC) and minimal bacteriocidal concentration (MBC) were determined to evaluate the antibacterial activity of TPP. The effects of TPP on biofilm formation were quantified by crystal violet staining, and the content of extracellular polysaccharides in the biofilm was determined by the phenol-sulfuric acid assay. the strain resistance to TPP was examined. [Results] TPP exhibited inhibitory effects on the three strains tested, with a MIC of 15.63 μg/mL for the three strains and a MBC of 125.00 μg/mL for both S. aureus and S. subsp. aureus. However, TPP was unable to kill MRSA even at a concentration of 125.00 μg/mL. The biofilm inhibition rates of TPP at MIC were as high as 72.9%, 69.2%, and 71.8% for the three strains, respectively. The content of extracellular polysaccharides decreased with the increase in the concentration of TPP. S. aureus did not develop resistance to TPP after 20 generations. [Conclusion] This study clarified the antibacterial performance of TPP, providing a theoretical basis for the further development and utilization of TPP in the medicine field.