N-Chloro-2,2-dimethyltaurines: a new class of remarkably stable N-chlorotaurines

Wang, Lu; Khosrovi, Behzad; Najafi, Ramin

doi:10.1016/j.tetlet.2008.02.038

Cited by 27 publications

(24 citation statements)

References 19 publications

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“…Scores of inflammation and the time to healing were also significantly improved by NCT compared to a standard therapy in treatment of external otitis (18) and to placebo in treatment of epidemic keratoconjunctivitis (21,22). Inspired by the usefulness of NCT, dimethylated derivatives of NCT (N-chloro-2,2-dimethyltaurine [DM-NCT] [23][24][25] and N,N-dichloro-2,2-dimethyltaurine [DM-NDCT] [5,26]), which are analogs of natural compounds and attract attention by improved stability, have been introduced.…”

Section: Active Halogen Compoundsmentioning

confidence: 99%

“…Examples are NCT (49) and the N-monochloro and N,N-dichloro derivatives of 2,2-dimethyltaurine (DM-NCT, DM-NDCT) (5,25,26,50). As sodium sulfonates, not only the compound itself but also all species originating from hydrolysis, protonation, and disproportionation are well soluble in the whole pH range (5,26,33). This is in contrast to other chloramines, e.g., chloramine T, which-as a sodium salt-is well soluble in water at pH Ͼ 6, while the only slightly soluble free acid is formed in acidic milieu (see equation 14) (42).…”

Section: Choosing Suitable Candidates For Anti-infective Applicationmentioning

confidence: 99%

“…NCT, DM-NCT, and DM-NDCT are easily accessible and therefore important candidates for practical use. While NCT is a body's own (natural) compound with the disadvantage of slightly reduced stability (33), DM-NCT and DM-NDCT have long-term stability in solution (5,24,26) and are analogs of natural compounds. NCT was investigated for nearly 15 years, and its anti-infective usefulness has been confirmed to date by numerous studies (reviewed in reference 49).…”

Section: Choosing Suitable Candidates For Anti-infective Applicationmentioning

confidence: 99%

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N -Chloramines, a Promising Class of Well-Tolerated Topical Anti-Infectives

Gottardi

Debabov

Nagl

2013

Antimicrob Agents Chemother

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Antibiotic resistance is a growing public health crisis. To address the development of bacterial resistance, the use of antibiotics has to be minimized for nonsystemic applications in humans, as well as in animals and plants. Possible substitutes with low potential for developing resistance are active chlorine compounds that have been in clinical use for over 180 years. These agents are characterized by pronounced differences in their chlorinating and/or oxidizing activity, with hypochlorous acid (HOCl) as the strongest and organic chloramines as the weakest members. Bacterial killing in clinical practice is often associated with unwanted side effects such as chlorine consumption, tissue irritation, and pain, increasing proportionally with the chlorinating/oxidizing potency. Since the chloramines are able to effectively kill pathogens (bacteria, fungi, viruses, protozoa), their application as anti-infectives is advisable, all the more so as they exhibit additional beneficial properties such as destruction of toxins, degradation of biofilms, and anticoagulative and anti-inflammatory activities. Within the ample field of chloramines, the stable N-chloro derivatives of ß-aminosulfonic acids are most therapeutically advanced. Being available as sodium salts, they distinguish themselves by good solubility and absence of smell. Important representatives are N-chlorotaurine, a natural compound occurring in the human immune system, and novel mono-and dichloro derivatives of dimethyltaurine, which feature improved stability.

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Section: Active Halogen Compoundsmentioning

confidence: 99%

Section: Choosing Suitable Candidates For Anti-infective Applicationmentioning

confidence: 99%

Section: Choosing Suitable Candidates For Anti-infective Applicationmentioning

confidence: 99%

See 1 more Smart Citation

N -Chloramines, a Promising Class of Well-Tolerated Topical Anti-Infectives

Gottardi

Debabov

Nagl

2013

Antimicrob Agents Chemother

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“…NVC-422 (N,N-dichloro-2,2-dimethyltaurine) (20) is active against Gram-positive and Gram-negative bacteria (including drug-resistant pathogens), fungi, and viruses (21). NVC-422 mechanism-of-action studies (22) indicate that it kills microorganisms by inactivating proteins via oxidative modification of Met and Cys.…”

mentioning

confidence: 99%

“…The synthesis of NVC-422 has been described previously (20). The purity of NVC-422 was 99.83% by high-performance liquid chromatography (HPLC).…”

mentioning

confidence: 99%

No Decrease in Susceptibility to NVC-422 in Multiple-Passage Studies with Methicillin-Resistant Staphylococcus aureus, S. aureus, Pseudomonas aeruginosa, and Escherichia coli

D'Lima

Friedman

Wang

et al. 2012

Antimicrob Agents Chemother

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Twenty-five serial passages of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and 50 passages of methicillin-resistant Staphylococcus aureus resulted in no significant increase in NVC-422 MICs, while ciprofloxacin MICs increased 256-fold for E. coli and 32-fold for P. aeruginosa and S. aureus. Mupirocin, fusidic acid, and retapamulin MICs for MRSA increased 64-, 256-, and 16-fold, respectively. No cross-resistance to NVC-422 was observed with mupirocin-, fusidic acid-, and retapamulin-resistant strains. Multiple-passage studies determine the effect of selective pressure of antibiotics on microorganisms (15), resulting in cumulative acquisition of mutations at the genetic level (3,5,6,13). The development of resistance is a result of the frequency of mutation, the number and type of mutations required to express resistance, the potency and concentration of the treating drug, and other factors (9,10,14). Currently, there is an unmet medical need for novel antimicrobial agents that are effective against resistant pathogens (14, 18).NVC-422 (N,N-dichloro-2,2-dimethyltaurine) (20) is active against Gram-positive and Gram-negative bacteria (including drug-resistant pathogens), fungi, and viruses (21). NVC-422 mechanism-of-action studies (22) indicate that it kills microorganisms by inactivating proteins via oxidative modification of Met and Cys. This mechanism differentiates NVC-422 from antibiotics by attacking multiple targets, thereby making it highly unlikely for microorganisms to develop resistance.NVC-422 is currently in clinical development for impetigo, urinary catheter blockage and encrustation, and adenoviral conjunctivitis.In this study, we investigated the propensity of NVC-422 to select for resistance by passaging bacteria at subinhibitory concentrations. Representative organisms Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) were selected (1,3,12,17). Ciprofloxacin was selected as a broad-spectrum comparator. Mupirocin, fusidic acid, and retapamulin were selected as comparators against MRSA, as these antibiotics are used for the treatment of topical infections (6,18,19).The synthesis of NVC-422 has been described previously (20). The purity of NVC-422 was 99.83% by high-performance liquid chromatography (HPLC). The stabilities of NVC-422 (100 g/ ml) in cation-adjusted Mueller-Hinton broth (CAMHB) and M9 minimal medium were tested at 37°C using the Agilent HPLC-1200 system (Agilent Technologies, Palo Alto, CA) with a diode array UV detector.E. coli ATCC 25922, S. aureus ATCC 29213, and MRSA ATCC 33591 were purchased from the American Type Culture Collection (ATCC, Manassas, VA); P. aeruginosa PAO1 was obtained from Queen's University (Kingston, Ontario, Canada). All strains were grown on tryptic soy agar (Difco Laboratories, Detroit, MI) at 37°C. Antibiotics were obtained from MP Biomedical (Santa Ana, CA), Sigma-Aldrich (St. Louis, MO), and APAC Pharmaceuticals, LLC (Columbia, MD).Determination of MICs was in accordance wit...

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Irrigation with N,N-dichloro-2,2-dimethyltaurine (NVC-422) in a citrate buffer maintains urinary catheter patency in vitro and prevents encrustation by Proteus mirabilis

et al. 2015

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Long-term use of indwelling urinary catheters can lead to urinary tract infections and loss of catheter patency due to encrustation and blockage. Encrustation of urinary catheters is due to formation of crystalline biofilms by urease-producing microorganisms such as Proteus mirabilis. An in vitro catheter biofilm model (CBM) was used to evaluate current methods for maintaining urinary catheter patency. We compared antimicrobial-coated urinary Foley catheters, with both available catheter irrigation solutions and investigational solutions containing NVC-422 (N,N-dichloro-2,2-dimethyltaurine; a novel broad-spectrum antimicrobial). Inoculation of the CBM reactor with 10(8) colony-forming units of P. mirabilis resulted in crystalline biofilm formation in catheters by 48 h and blockage of catheters within 5 days. Silver hydrogel or nitrofurazone-coated catheters did not extend the duration of catheter patency. Catheters irrigated daily with commercially available solutions such as 0.25 % acetic acid and isotonic saline blocked at the same rate as untreated catheters. Daily irrigations of catheters with 0.2 % NVC-422 in 10 mM acetate-buffered saline pH 4 or Renacidin maintained catheter patency throughout 10-day studies, but P. mirabilis colonization of the CBM remained. In contrast, 0.2 % NVC-422 in citrate buffer (6.6 % citric acid at pH 3.8) resulted in an irrigation solution that not only maintained catheter patency for 10 days but also completely eradicated the P. mirabilis biofilm within one treatment day. These data suggest that an irrigation solution containing the rapidly bactericidal antimicrobial NVC-422 in combination with citric acid to permeabilize crystalline biofilm may significantly enhance catheter patency versus other approved irrigation solutions and antimicrobial-coated catheters.

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N-Chloro-2,2-dimethyltaurines: a new class of remarkably stable N-chlorotaurines

Cited by 27 publications

References 19 publications

N -Chloramines, a Promising Class of Well-Tolerated Topical Anti-Infectives

N -Chloramines, a Promising Class of Well-Tolerated Topical Anti-Infectives

No Decrease in Susceptibility to NVC-422 in Multiple-Passage Studies with Methicillin-Resistant Staphylococcus aureus, S. aureus, Pseudomonas aeruginosa, and Escherichia coli

Irrigation with N,N-dichloro-2,2-dimethyltaurine (NVC-422) in a citrate buffer maintains urinary catheter patency in vitro and prevents encrustation by Proteus mirabilis

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