During oxidative burst, neutrophils selectively generate HOCl to destroy invading microbial pathogens. Excess HOCl reacts with taurine, a semi-essential amino acid, resulting in the formation of the longer-lived biogenerated broad-spectrum antimicrobial agent, N-chlorotaurine (NCT). In the presence of an excess of HOCl or under moderately acidic conditions, NCT can be further chlorinated, or it can disproportionate to produce N,N-dichlorotaurine (NNDCT). In the present study, 2,2-dimethyltaurine was used to prepare a more stable N-chlorotaurine, namely, N,N-dichloro-2,2-dimethyltaurine (NVC-422). In addition, we report on the chemical characterization, in vitro antimicrobial properties, and cytotoxicity of this compound. NVC-422 was shown effectively to kill all 17 microbial strains tested, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium. The minimum bactericidal concentration of NVC-422 against Gram-negative and Grampositive bacteria ranged from 0.12 to 4 g/ml. The minimum fungicidal concentrations against Candida albicans and Candida glabrata were 32 and 16 g/ml, respectively. NVC-422 has an in vitro cytotoxicity (50% cytotoxicity ‫؍‬ 1,440 g/ml) similar to that of NNDCT. Moreover, our data showed that this agent possesses rapid, pH-dependent antimicrobial activity. At pH 4, NVC-422 completely killed both Escherichia coli and S. aureus within 5 min at a concentration of 32 g/ml. Finally, the effect of NVC-422 in the treatment of an E. coli-infected granulating wound rat model was evaluated. Treatment of the infected granulating wound with NVC-422 resulted in significant reduction of the bacterial tissue burden and faster wound healing compared to a saline-treated control. These findings suggest that NVC-422 could have potential application as a topical antimicrobial.As part of the innate immune system, leukocytes are capable of generating and releasing reactive oxygen species. During oxidative burst, neutrophils selectively generate hypochlorous acid to destroy invading microbial pathogens. In a secondary reaction, hypochlorous acid reacts with taurine, a semi-essential amino acid. The resulting N-chlorotaurine (NCT) is a wellknown antimicrobial and anti-inflammatory oxidant (12, 15). Furthermore, NCT has shown significant bactericidal and fungicidal properties with relatively low toxicity compared to other oxidants (13,14). In the presence of an excess of hypochlorous acid or under moderately acidic conditions, NCT can be further chlorinated or, alternatively, it can disproportionate to form N,N-dichlorotaurine (NNDCT), which also has broadspectrum antimicrobial activity (9). Unfortunately, both NCT and NNDCT have relatively short solution half-lives, decomposing by hydrolytic dehydrochlorination (5, 6, 16). Because of this instability, the potential usefulness of the endogenous Nchlorotaurines as marketable therapeutics is limited. Replacement of the hydrogens at the ␤-carbon of taurine by methyl groups prevents the dehydrochlorination process, thereby circumventing this instabi...

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Wound healing depends on controlling bacterial balance while maintaining the viability of the healing tissues. In vitro toxicity indexes provide helpful guidelines subsequent to in vivo evaluations and clinical applications. The study findings suggest that NeutroPhase, in contrast with many commercially available wound cleansers, has rapid bactericidal activity at concentrations that are safe for human cells.

NVC-422 is an effective topical agent against S. aureus biofilms, with dose-dependent efficacy in this animal model of biofilm-associated sinusitis.