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D. C. Paik, S. M. Modak, Q. Wen; Aliphatic β-Nitroalcohols for Therapeutic Corneoscleral Cross-Linking: Antimicrobial Effects. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2424.
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© ARVO (1962-2015); The Authors (2016-present)
Our recent studies have raised the possibility of using aliphatic β-nitro alcohols (BNAs) for pharmacologic, therapeutic cross-linking. However, such BNAs are also known to possess anti-microbial effects. Thus, the present study was performed in order to compare the relative microbial killing efficacy of three BNAs, a mono-, di-, and tri-nitroalcohol.
The antibacterial and antifungal activity at pH 7.4 was evaluated for 2-nitro-1-propanol (monol), 2-methyl-2-nitro-1,3-propanediol (diol), and 2-hydroxymethyl-2-nitro-1,3-propanediol (triol), in a proteinaceous media simulating an in vivo environment. Trypticase Soy broth was inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, or Candida albicans (ATCC - Manassas, VA), incubated, and serially diluted to obtain 106cfu of organisms/ml. The culture was then mixed with bovine adult serum (1:1 ratio), followed by the addition of BNA solution (100mM). After incubation at 370C for 3 hrs, drug neutralizing buffer was added, and the mixture plated on Trypticase Soy agar. The number of cfu was then counted following a 24 hrs growth period. At least three independent determinations were performed for each group.
Against S. aureus, the log10 growth reductions were 0, 3.6, and 6.9 (control growth 6.9) corresponding to % growth reductions of 0, 99.94, and >99.99 for the monol, diol, and triol, respectively. Against P. aeruginosa, the log10 growth reductions were 6.1, 6.1, and 6.1 (control growth 6.1) corresponding to % growth reductions of >99.99 for all three compounds. Against C. albicans, the log10 growth reductions were 5.4, 0.8, and 5.1 (control growth 5.4) corresponding to >99.99, 15.0, and 99.99 for the monol, diol, and triol, respectively..
BNAs exhibit a differential microbicidal effect against strains of bacteria and fungus. The triol and diol were effective against S. aureus. All three compounds were equally effective against P. aeruginosa, and the triol and monol were effective against C. albicans. These studies underscore an exciting new possibility for the use of these agents in clinical therapeutics (i.e. infectious diseases).
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