To synthesize and assess the antimicrobial and antiadhesive properties of oxazaborolidines derivatives (a boron containing compound which resemble auto-inducer 2 (AI-2))
Methods:
*The oxazaborolidines were synthesized by the reaction of amino alcohol, using (-)-ephedrine and (-)-norpseudoephedrine or diol amine and boronic acid, with the azeotropic removal of water. *The compounds were characterized using 1H, 13C and 11B NMR, Microanalysis and mass spectroscopy. *The MIC was determined as follows: microculture dishes were used to determine MIC of eight derivatives of oxazaborolidines. Each well contained brain heart infusion medium, overnight suspension of S. mutans ATCC 27351 and the tested compound. Each compound was tested at five different concentrations between 0-50 mM.. These cultures were incubated at 370C in atmosphere enriched in 5% CO2 for 24 hours. Bacteria growth was determined as turbidity by computerized ELISA reader * Anti-adhesion effect was determined by incubating pre-labeled radioactive bacteria with hydroxyapatite (HA), Sucrose, and oxazaborolidine derivative (at various concentration) for one hour at 370C with gentle rotation, The amount of the adsorbed labeled bacteria on HA was measured using β-counter.
Results: The synthesized compound that contained both the N-Methyl and B-Butyl groups was the most antibacterial active, MIC = 0.53 mM. Structure-activity relationship (SAR), between compounds and anti-adhesive properties was observed. Compound that contained B-Butyl group shows significant anti-adhesive effect (~70%), while replacing the butyl by phenyl group led to adverse effect (Increased adhesion by ~60%)
Conclusion: Oxazaborolidines can affect biofilm formation on two levels: antibacterial and anti-adhesion. A clear dose-response and SAR has been observed.